E G Lakatta

Summary

Affiliation: National Institutes of Health
Country: USA

Publications

  1. ncbi request reprint Cardiovascular aging in health
    E G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Clin Geriatr Med 16:419-44. 2000
  2. pmc Role of inflammation in the pathogenesis of arterial stiffness
    Sungha Park
    Division of Cardiology, Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea
    Yonsei Med J 53:258-61. 2012
  3. ncbi request reprint Beta-adrenergic stimulation modulation of heart rate via synchronization of ryanodine receptor Ca2+ release
    Edward G Lakatta
    Laboratory of Cardiovascular Science, NIA Intramural Research Program, Gerontology Research Center, National Institute on Aging National Institute of Health, Baltimore, Maryland 21224, USA
    J Card Surg 17:451-61. 2002
  4. ncbi request reprint Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Heart Fail Rev 7:29-49. 2002
  5. pmc Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Med Clin North Am 93:583-604, Table of Contents. 2009
  6. ncbi request reprint Perspectives on mammalian cardiovascular aging: humans to molecules
    Edward G Lakatta
    Laboratory of Cardiovascular Science, NIA Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Comp Biochem Physiol A Mol Integr Physiol 132:699-721. 2002
  7. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, Gerontology Research Center, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:139-46. 2003
  8. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:346-54. 2003
  9. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:490-7. 2003
  10. ncbi request reprint Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state
    Konstantin Y Bogdanov
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 99:979-87. 2006

Collaborators

Detail Information

Publications113 found, 100 shown here

  1. ncbi request reprint Cardiovascular aging in health
    E G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Clin Geriatr Med 16:419-44. 2000
    ..The Baltimore Longitudinal Study on Aging has made an effort to characterize the effects of aging on multiple aspects of cardiovascular structure and function. The concepts that have evolved from this and other studies are discussed...
  2. pmc Role of inflammation in the pathogenesis of arterial stiffness
    Sungha Park
    Division of Cardiology, Cardiovascular Center, Yonsei University College of Medicine, Seoul, Korea
    Yonsei Med J 53:258-61. 2012
    ....
  3. ncbi request reprint Beta-adrenergic stimulation modulation of heart rate via synchronization of ryanodine receptor Ca2+ release
    Edward G Lakatta
    Laboratory of Cardiovascular Science, NIA Intramural Research Program, Gerontology Research Center, National Institute on Aging National Institute of Health, Baltimore, Maryland 21224, USA
    J Card Surg 17:451-61. 2002
    ..An overview of these recent results, which provides novel insights into mechanisms of cardiac reserve that underlie the "fight or flight instinct, is presented here...
  4. ncbi request reprint Age-associated cardiovascular changes in health: impact on cardiovascular disease in older persons
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Heart Fail Rev 7:29-49. 2002
    ..Observations from relevant experiments in animal models have been integrated with those in humans to provide possible mechanistic insight...
  5. pmc Arterial aging and subclinical arterial disease are fundamentally intertwined at macroscopic and molecular levels
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Med Clin North Am 93:583-604, Table of Contents. 2009
    ....
  6. ncbi request reprint Perspectives on mammalian cardiovascular aging: humans to molecules
    Edward G Lakatta
    Laboratory of Cardiovascular Science, NIA Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Comp Biochem Physiol A Mol Integr Physiol 132:699-721. 2002
    ..Overall, these changes lead to a diminished (but not necessarily exhausted) capacity of the heart to adapt to physiological or pathological stress with advancing age...
  7. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, Gerontology Research Center, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:139-46. 2003
  8. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part II: the aging heart in health: links to heart disease
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:346-54. 2003
  9. ncbi request reprint Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part III: cellular and molecular clues to heart and arterial aging
    Edward G Lakatta
    Gerontology Research Center, Intramural Research Program, Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Circulation 107:490-7. 2003
  10. ncbi request reprint Membrane potential fluctuations resulting from submembrane Ca2+ releases in rabbit sinoatrial nodal cells impart an exponential phase to the late diastolic depolarization that controls their chronotropic state
    Konstantin Y Bogdanov
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 99:979-87. 2006
    ....
  11. ncbi request reprint The integration of spontaneous intracellular Ca2+ cycling and surface membrane ion channel activation entrains normal automaticity in cells of the heart's pacemaker
    Edward G Lakatta
    National Institute on Aging, Gerontology Research Center, Intramural Research Program, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Ann N Y Acad Sci 1080:178-206. 2006
    ....
  12. ncbi request reprint Beyond Bowditch: the convergence of cardiac chronotropy and inotropy
    Edward G Lakatta
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Cell Calcium 35:629-42. 2004
    ....
  13. ncbi request reprint The "heartbreak" of older age
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Mol Interv 2:431-46. 2002
  14. pmc A coupled SYSTEM of intracellular Ca2+ clocks and surface membrane voltage clocks controls the timekeeping mechanism of the heart's pacemaker
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 106:659-73. 2010
    ..This review examines evidence that forms the basis of this coupled-clock system concept in cardiac SANCs...
  15. ncbi request reprint Cyclic variation of intracellular calcium: a critical factor for cardiac pacemaker cell dominance
    Edward G Lakatta
    Gerontology Research Center, Baltimore, MD 21224, USA
    Circ Res 92:e45-50. 2003
    ..The full text of this article is available at http://www.circresaha.org...
  16. pmc Age-associated reductions in cardiac beta1- and beta2-adrenergic responses without changes in inhibitory G proteins or receptor kinases
    R P Xiao
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland 21224, USA
    J Clin Invest 101:1273-82. 1998
    ..Neither GRKs nor Gi proteins appear to contribute to the age-associated reduction in cardiac beta-AR responsiveness...
  17. ncbi request reprint Recent advances in cardiac beta(2)-adrenergic signal transduction
    R P Xiao
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224, USA
    Circ Res 85:1092-100. 1999
    ....
  18. pmc Synergism of coupled subsarcolemmal Ca2+ clocks and sarcolemmal voltage clocks confers robust and flexible pacemaker function in a novel pacemaker cell model
    Victor A Maltsev
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Am J Physiol Heart Circ Physiol 296:H594-615. 2009
    ..In conclusion, the Ca(2+) clock is a new critical dimension in SANC function. A synergism of the coupled function of Ca(2+) and membrane clocks confers fail-safe SANC operation at greatly varying rates...
  19. ncbi request reprint Coupling of beta2-adrenoceptor to Gi proteins and its physiological relevance in murine cardiac myocytes
    R P Xiao
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, MD, USA
    Circ Res 84:43-52. 1999
    ....
  20. ncbi request reprint High basal protein kinase A-dependent phosphorylation drives rhythmic internal Ca2+ store oscillations and spontaneous beating of cardiac pacemaker cells
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224 6825, USA
    Circ Res 98:505-14. 2006
    ....
  21. ncbi request reprint Sinoatrial nodal cell ryanodine receptor and Na(+)-Ca(2+) exchanger: molecular partners in pacemaker regulation
    K Y Bogdanov
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
    Circ Res 88:1254-8. 2001
    ....
  22. ncbi request reprint Endogenous Na,K pump ligands are differentially regulated during acute NaCl loading of Dahl rats
    O V Fedorova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, MD 21224, USA
    Circulation 102:3009-14. 2000
    ..We compared regulation of MBG and OLC by acute NaCl loading in Dahl salt-sensitive (DS) and salt-resistant (DR) rats...
  23. ncbi request reprint The emergence of a general theory of the initiation and strength of the heartbeat
    Victor A Maltsev
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
    J Pharmacol Sci 100:338-69. 2006
    ....
  24. ncbi request reprint Phosphatidylinositol 3-kinase offsets cAMP-mediated positive inotropic effect via inhibiting Ca2+ influx in cardiomyocytes
    Veronique Leblais
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, Baltimore, MD 21224, USA
    Circ Res 95:1183-90. 2004
    ....
  25. ncbi request reprint Ca(2+) signaling in cardiac myocytes overexpressing the alpha(1) subunit of L-type Ca(2+) channel
    Long Sheng Song
    Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Circ Res 90:174-81. 2002
    ..These results also suggest that a modest but sustained increase in Ca(2+) influx triggers a coordinated remodeling of Ca(2+) handling to maintain Ca(2+) homeostasis...
  26. pmc Cholinergic receptor signaling modulates spontaneous firing of sinoatrial nodal cells via integrated effects on PKA-dependent Ca(2+) cycling and I(KACh)
    Alexey E Lyashkov
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224 6825, USA
    Am J Physiol Heart Circ Physiol 297:H949-59. 2009
    ....
  27. ncbi request reprint beta-Adrenergic stimulation synchronizes intracellular Ca(2+) release during excitation-contraction coupling in cardiac myocytes
    L S Song
    Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
    Circ Res 88:794-801. 2001
    ....
  28. ncbi request reprint Expanded blood volumes contribute to the increased cardiovascular performance of endurance-trained older men
    J M Hagberg
    Division of Gerontology, Department of Medicine, University of Maryland School of Medicine, Geriatrics Service and Geriatric Research, Education, and Clinical Center, Baltimore Veterans Administration Medical Center, Baltimore, MD 21201, USA
    J Appl Physiol (1985) 85:484-9. 1998
    ....
  29. ncbi request reprint Ca2+/calmodulin kinase II-dependent phosphorylation of ryanodine receptors suppresses Ca2+ sparks and Ca2+ waves in cardiac myocytes
    Dongmei Yang
    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA
    Circ Res 100:399-407. 2007
    ....
  30. ncbi request reprint Calcium cycling protein density and functional importance to automaticity of isolated sinoatrial nodal cells are independent of cell size
    Alexey E Lyashkov
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, Baltimore, Maryland 21224 6825, USA
    Circ Res 100:1723-31. 2007
    ..Because normal automaticity of these cells requires intact Ca(2+) cycling, interactions of SERCA, RyR2 and NCX molecules are implicated in the initiation of the SAN impulse...
  31. ncbi request reprint beta2-adrenergic cAMP signaling is uncoupled from phosphorylation of cytoplasmic proteins in canine heart
    M Kuschel
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, MD, USA
    Circulation 99:2458-65. 1999
    ....
  32. ncbi request reprint Ca2+ signalling between single L-type Ca2+ channels and ryanodine receptors in heart cells
    S Q Wang
    Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Nature 410:592-6. 2001
    ..This optical analysis of single-channel communication affords a powerful means for elucidating Ca2+-signalling mechanisms at the molecular level...
  33. pmc Termination of Ca2+ release by a local inactivation of ryanodine receptors in cardiac myocytes
    J S Sham
    Division of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institutions, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 95:15096-101. 1998
    ..These results indicate that Ca2+ release is terminated primarily by a highly localized, use-dependent inactivation of RyRs but not by the stochastic closing or adaptation of RyRs in intact ventricular myocytes...
  34. doi request reprint The missing link in the mystery of normal automaticity of cardiac pacemaker cells
    Edward G Lakatta
    National Institutes of Health, National Institute on Aging, Laboratory of Cardiovascular Science, Baltimore, MD 21224, USA
    Ann N Y Acad Sci 1123:41-57. 2008
    ....
  35. ncbi request reprint Impact of age on the cardiovascular response to dynamic upright exercise in healthy men and women
    J L Fleg
    Laboratory of Cardiovascular Science, Johns Hopkins University School of Medicine, Baltimore, Maryland 21224, USA
    J Appl Physiol (1985) 78:890-900. 1995
    ..Thus, age and gender each have a significant impact on the cardiac response to exhaustive upright cycle exercise...
  36. pmc Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats
    Mingyi Wang
    Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, 3 B 03, Baltimore, MD 21224 6825, USA
    Am J Pathol 167:1429-42. 2005
    ..Thus, Ang II-induced effects on MMP2, transforming growth factor-beta1, collagen, and VSMCs are central to the arterial remodeling that accompanies advancing age...
  37. pmc Diastolic calcium release controls the beating rate of rabbit sinoatrial node cells: numerical modeling of the coupling process
    Victor A Maltsev
    Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6825, USA
    Biophys J 86:2596-605. 2004
    ..The model predicts that the diastolic Ca2+ release strongly interacts with plasma membrane via INaCa and thus controls the phase of the action potential upstroke and ultimately the final action potential rate...
  38. pmc The sex-specific impact of systolic hypertension and systolic blood pressure on arterial-ventricular coupling at rest and during exercise
    Paul D Chantler
    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21225, USA
    Am J Physiol Heart Circ Physiol 295:H145-53. 2008
    ..Whether a smaller E(a)I/E(LV)I reserve leads to functional limitations warrants further examination...
  39. pmc Arterial-ventricular coupling: mechanistic insights into cardiovascular performance at rest and during exercise
    Paul D Chantler
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 3001 S Hanover Street, Baltimore, MD 21225, USA
    J Appl Physiol (1985) 105:1342-51. 2008
    ..We discuss these effects both at rest and during exercise and highlight the mechanistic insights that can be derived from studying E(A)/E(LV)...
  40. ncbi request reprint Pharmacological stimulation of beta2-adrenergic receptors (beta2AR) enhances therapeutic effectiveness of beta1AR blockade in rodent dilated ischemic cardiomyopathy
    Ismayil Ahmet
    The Laboratory of Cardiovascular Sciences, Intramural Research Program, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224 6825, USA
    Heart Fail Rev 10:289-96. 2005
    ..Here we investigate whether the addition of chronic pharmacological beta2AR stimulation enhances the therapeutic effects of beta1AR blockade on cardiac remodeling in the same model...
  41. ncbi request reprint Marinobufagenin, an endogenous ligand of alpha-1 sodium pump, is a marker of congestive heart failure severity
    Alexander I Fridman
    Laboratory of Cardiovascular Science, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Hypertens 20:1189-94. 2002
    ....
  42. pmc Milk fat globule protein epidermal growth factor-8: a pivotal relay element within the angiotensin II and monocyte chemoattractant protein-1 signaling cascade mediating vascular smooth muscle cells invasion
    Zongming Fu
    Laboratory of Cardiovascular Science, National Institute on Aging National Institutes of Health, Baltimore, MD 21224, USA
    Circ Res 104:1337-46. 2009
    ..Thus, targeting of MFG-E8 within this signaling axis pathway is a potential novel therapy for the prevention and treatment of the age-associated vascular diseases such as atherosclerosis...
  43. pmc Endogenous sodium pump inhibitors and age-associated increases in salt sensitivity of blood pressure in normotensives
    David E Anderson
    Laboratory on Cardiovascular Science, National Institute on Aging, Intramural Research Program, Gerontology Research Center, Baltimore, MD 21224 6825, USA
    Am J Physiol Regul Integr Comp Physiol 294:R1248-54. 2008
    ....
  44. pmc G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels
    Y Chen-Izu
    Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224 6823, USA
    Biophys J 79:2547-56. 2000
    ..Our results suggest that the dual coupling of beta(2)-AR to both G(s)- and G(i)-proteins leads to a highly localized beta(2)-AR signaling pathway to modulate sarcolemmal L-type Ca(2+) channels in rat ventricular myocytes...
  45. pmc Amplitude distribution of calcium sparks in confocal images: theory and studies with an automatic detection method
    H Cheng
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Biophys J 76:606-17. 1999
    ..In addition, we discuss possible situations when a modal distribution might be observed...
  46. ncbi request reprint Rhythmic Ca2+ oscillations drive sinoatrial nodal cell pacemaker function to make the heart tick
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, NIH, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Ann N Y Acad Sci 1047:138-56. 2005
    ..Ca(2+) cycling via the SR Ca(2+) pump, RyR and NCX, and its modulation by beta-AR stimulation is, therefore, a general mechanism of cardiac chronotropy and inotropy...
  47. pmc Ca(2+) -stimulated basal adenylyl cyclase activity localization in membrane lipid microdomains of cardiac sinoatrial nodal pacemaker cells
    Antoine Younes
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, Intramural Research Program, NIH, Baltimore, MD 21224, USA
    J Biol Chem 283:14461-8. 2008
    ..This feed forward "fail safe" system, kept in check by a high basal phosphodiesterase activity, is central to the generation of normal rhythmic, spontaneous action potentials by pacemaker cells...
  48. pmc A novel quantitative explanation for the autonomic modulation of cardiac pacemaker cell automaticity via a dynamic system of sarcolemmal and intracellular proteins
    Victor A Maltsev
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Am J Physiol Heart Circ Physiol 298:H2010-23. 2010
    ..In conclusion, our model simulations corroborate recent experimental results in rabbit SANCs pointing to a new paradigm for GPCR heart rate modulation by a complex system of dynamically coupled sarcolemmal and intracellular proteins...
  49. ncbi request reprint Dynamic interactions of an intracellular Ca2+ clock and membrane ion channel clock underlie robust initiation and regulation of cardiac pacemaker function
    Victor A Maltsev
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD, USA
    Cardiovasc Res 77:274-84. 2008
    ..Both basal and reserve protein kinaseA-dependent phosphorylation of Ca(2+) cycling proteins control the speed and amplitude of SR Ca(2+) cycling to regulate the beating rate by strongly coupled Ca(2+) and M clocks...
  50. ncbi request reprint Attenuated cardiovascular reserve during prolonged submaximal cycle exercise in healthy older subjects
    Luis C L Correia
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
    J Am Coll Cardiol 40:1290-7. 2002
    ..The goal of this study was to determine the effect of age on the hemodynamic response to prolonged submaximal aerobic exercise in healthy volunteers...
  51. ncbi request reprint Endogenous ligand of alpha(1) sodium pump, marinobufagenin, is a novel mediator of sodium chloride--dependent hypertension
    Olga V Fedorova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Circulation 105:1122-7. 2002
    ....
  52. ncbi request reprint Cardiovascular reserve capacity in healthy older humans
    E G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, MD 21224
    Aging (Milano) 6:213-23. 1994
    ..The exercise heart rate deficit that occurs with aging, however, is not affected by physical conditioning...
  53. ncbi request reprint Improved arterial compliance by a novel advanced glycation end-product crosslink breaker
    D A Kass
    Division of Cardiology, The Johns Hopkins Medical Institutions, Baltimore, MD 21287, USA
    Circulation 104:1464-70. 2001
    ..We tested whether ALT-711, a novel nonenzymatic breaker of advanced glycation end-product crosslinks, selectively improves arterial compliance and lowers pulse pressure in older individuals with vascular stiffening...
  54. pmc A cross-link breaker has sustained effects on arterial and ventricular properties in older rhesus monkeys
    P V Vaitkevicius
    Intramural Research Program, Gerontology Research Center, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224, USA
    Proc Natl Acad Sci U S A 98:1171-5. 2001
    ....
  55. ncbi request reprint Temporal dynamics of inotropic, chronotropic, and metabolic responses during beta1- and beta2-AR stimulation in the isolated, perfused rat heart
    P McConville
    Nuclear Magnetic Resonance Unit, Laboratory of Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Am J Physiol Endocrinol Metab 289:E412-8. 2005
    ..However, a similar decrease in intracellular energy charge was seen in the two groups, consistent with a greater rate of oxidative phosphorylation during beta1- than during beta2-AR stimulation...
  56. ncbi request reprint Marinobufagenin, an endogenous alpha-1 sodium pump ligand, in hypertensive Dahl salt-sensitive rats
    O V Fedorova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, Baltimore, MD, USA
    Hypertension 37:462-6. 2001
    ..MBG acts as a selective inhibitor of the ouabain-resistant alpha-1 Na(+)/K(+)-ATPase subunit, ie, the major sodium pump isoform of the kidneys, as would be expected of a putative natriuretic hormone...
  57. ncbi request reprint Upregulation of the nitric oxide-cGMP pathway in aged myocardium: physiological response to l-arginine
    S J Zieman
    Department of Medicine, Cardiology Division, Johns Hopkins Medical Institutions, and Gerontology Research Center, National Institute on Aging, Baltimore, MD, USA
    Circ Res 88:97-102. 2001
    ..l-Arginine, the NOS precursor, enhances ventricular relaxation in old and young hearts, indicating that the NOS pathway may be exploited to modulate diastolic function in aged myocardium...
  58. ncbi request reprint Interaction of NaCl and behavioral stress on endogenous sodium pump ligands in rats
    O V Fedorova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Am J Physiol Regul Integr Comp Physiol 281:R352-8. 2001
    ..Aortic weights were increased in Iso and Iso+Salt. Thus a high NaCl intake stimulates MBG excretion, whereas isolation stress stimulates OLC. The combination of Salt and Iso is accompanied by marked stimulation of both SPL...
  59. ncbi request reprint Potential paracrine role of the pericardium in the regulation of cardiac function
    A Mebazaa
    Department of Anesthesiology and Critical Care Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21287 3711, USA
    Cardiovasc Res 40:332-42. 1998
    ..Both coronary and endocardial endothelium regulate cardiac contractile function via paracrine pathways. We investigated whether pericardial fluid (PF) and pericardial mesothelial cells (PMC) could exert a similar paracrine action...
  60. pmc Ion concentration-dependence of rat cardiac unitary L-type calcium channel conductance
    A Guia
    Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Biophys J 80:2742-50. 2001
    ..This study leads to future work on the molecular basis of E-C coupling with a physiological concentration of Ca ions permeating the Ca channel...
  61. ncbi request reprint Differences in the bioenergetic response of the isolated perfused rat heart to selective beta1- and beta2-adrenergic receptor stimulation
    Patrick McConville
    NMR Unit, Laboratory of Clinical Investigation, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Circulation 107:2146-52. 2003
    ..In the heart, striking functional differences exist after stimulation of the beta1- and beta2-adrenergic receptor (AR) subtypes. These may be linked to differences in metabolic response during beta1- and beta2-AR stimulation...
  62. ncbi request reprint Myocardial PKC beta2 and the sensitivity of Na/K-ATPase to marinobufagenin are reduced by cicletanine in Dahl hypertension
    Olga V Fedorova
    Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA
    Hypertension 41:505-11. 2003
    ..Thus, PKC-induced phosphorylation of cardiac alpha-1 Na/K-ATPase is a likely target for cicletanine treatment...
  63. ncbi request reprint Cardiovascular features of heart failure with preserved ejection fraction versus nonfailing hypertensive left ventricular hypertrophy in the urban Baltimore community: the role of atrial remodeling/dysfunction
    Vojtech Melenovsky
    Division of Cardiology, Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA
    J Am Coll Cardiol 49:198-207. 2007
    ....
  64. pmc Sarcoplasmic reticulum Ca2+ pumping kinetics regulates timing of local Ca2+ releases and spontaneous beating rate of rabbit sinoatrial node pacemaker cells
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 107:767-75. 2010
    ..The LCR period, ie, a delay between AP-induced Ca(2+) transient and LCR appearance, defines the time of late diastolic depolarization I(NCX) activation. Mechanisms that control the LCR period, however, are still unidentified...
  65. doi request reprint Cardioprotective and survival benefits of long-term combined therapy with beta2 adrenoreceptor (AR) agonist and beta1 AR blocker in dilated cardiomyopathy postmyocardial infarction
    Ismayil Ahmet
    National Institute on Aging, Intramural Research Program, Gerontology Research Center, 5600 Nathan Shock Drive, Baltimore, MD 21224 6825, USA
    J Pharmacol Exp Ther 325:491-9. 2008
    ..The results demonstrate the cardioprotective and survival benefit of long-term combination therapy of beta2 AR agonists and beta1 AR blockers in a model of DCM...
  66. ncbi request reprint Beneficial effects of chronic pharmacological manipulation of beta-adrenoreceptor subtype signaling in rodent dilated ischemic cardiomyopathy
    Ismayil Ahmet
    Gerontology Research Center, Baltimore, MD 21224, USA
    Circulation 110:1083-90. 2004
    ..We hypothesized that prolonged beta(2)AR stimulation or beta1AR blockade would each protect myocytes from death and thereby ameliorate cardiac remodeling in chronic heart failure...
  67. ncbi request reprint Action potential prolongation in cardiac myocytes of old rats is an adaptation to sustain youthful intracellular Ca2+ regulation
    Andrzej M Janczewski
    Laboratory of Cardiovascular Science, Gerontology Research Center, Intramural Research Program, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224 6823, USA
    J Mol Cell Cardiol 34:641-8. 2002
    ..These results suggest that ventricular myocytes of old rats utilize AP prolongation to preserve an optimal SR Ca2+ loading, CICR gain and relaxation of Ca2+(i) transients...
  68. pmc Dilated cardiomyopathy with increased SR Ca2+ loading preceded by a hypercontractile state and diastolic failure in the alpha(1C)TG mouse
    Su Wang
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA
    PLoS ONE 4:e4133. 2009
    ..Thus, the dilated cardiomyopathy that evolves in this mouse model exhibits signs of both systolic and diastolic failure, but not a deficient SR Ca2+ loading or release, as occurs in some other cardiomyopathic models...
  69. ncbi request reprint Effect of estrogen and progestin replacement on arterial stiffness indices in postmenopausal women
    A Scuteri
    Gerontology Research Center, National Institute on Aging National Institutes of Health, Baltimore, Maryland 21224, USA
    Aging (Milano) 13:122-30. 2001
    ..In conclusion, ERT in postmenopausal women can beneficially affect the vascular system, by reducing BP and the age-associated increase in arterial stiffness. The addition of progestins to ERT may reduce these beneficial effects...
  70. ncbi request reprint Rapamycin inhibits alpha 1-adrenergic receptor-stimulated cardiac myocyte hypertrophy but not activation of hypertrophy-associated genes. Evidence for involvement of p70 S6 kinase
    M O Boluyt
    Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, MD 21224, USA
    Circ Res 81:176-86. 1997
    ..Our results demonstrate that intracellular signaling pathways responsible for transcriptional and translational responses diverge early after alpha 1-AR stimulation in cardiac myocytes...
  71. pmc Elevated mineralocorticoid receptor activity in aged rat vascular smooth muscle cells promotes a proinflammatory phenotype via extracellular signal-regulated kinase 1/2 mitogen-activated protein kinase and epidermal growth factor receptor-dependent pathwa
    Alexander W Krug
    National Institutes of Health, National Institute on Aging, Laboratory of Cardiovascular Science, Baltimore, MD 21224, USA
    Hypertension 55:1476-83. 2010
    ....
  72. pmc Arterial aging is risky
    Edward G Lakatta
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging Intramural Research Program, National Institutes of Health, Baltimore, MD 21224, USA
    J Appl Physiol 105:1321-2. 2008
  73. ncbi request reprint Differential response of cardiac fibroblasts from young adult and senescent rats to ANG II
    K Shivakumar
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Am J Physiol Heart Circ Physiol 284:H1454-9. 2003
    ..Such age-related modification of the response of cardiac fibroblasts to ANG II may counteract the effects of augmented intracardiac ANG II production in the senescent heart, limiting fibrogenesis...
  74. ncbi request reprint Effect of light-to-moderate alcohol consumption on age-associated arterial stiffening
    Hidetaka Hougaku
    Clinical Research Branch, Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21225, USA
    Am J Cardiol 95:1006-10. 2005
    ..A U-shaped relation was found between alcohol intake and a stiffness index, with the lowest index in moderate drinkers, which may partially explain the relation between alcohol and cardiovascular disease...
  75. ncbi request reprint Walking may be related to less vascular stiffness in the Activity Counseling Trial (ACT)
    Richard J Havlik
    Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
    Am Heart J 150:270-5. 2005
    ..The effects of the interventions, as well as the impact of walking and correlates such as older age and maximal oxygen uptake (VO2max), on APWV were assessed...
  76. ncbi request reprint Heterodimerization of beta1- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility
    Wei Zhong Zhu
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA
    Circ Res 97:244-51. 2005
    ....
  77. pmc Normal heart rhythm is initiated and regulated by an intracellular calcium clock within pacemaker cells
    Victor A Maltsev
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, 5600 Nathan Shock Drive, Baltimore, MD 21224 6825, USA
    Heart Lung Circ 16:335-48. 2007
    ....
  78. ncbi request reprint Greater glycogen utilization during 1- than 2-adrenergic receptor stimulation in the isolated perfused rat heart
    Patrick McConville
    Laboratory of Clinical Investigation, Box 29, Gerontology Research Center 4D 08, 5600 Nathan Shock Dr, Baltimore, MD 21 224, USA
    Am J Physiol Endocrinol Metab 293:E1828-35. 2007
    ..These findings are consistent with beta(1)-AR-specific PKA-dependent glycogen phosphorylase kinase signaling...
  79. ncbi request reprint Altered regulation of matrix metalloproteinase-2 in aortic remodeling during aging
    Mingyi Wang
    Laboratory of Cardiovascular Sciences, Gerontology Research Center, National Institute on Aging National Institutes of Health, Baltimore, MD 21224 6825, USA
    Hypertension 39:865-73. 2002
    ..These factors are candidate mechanisms for age-associated vascular remodeling, a potent risk factor for vascular diseases with advancing age...
  80. ncbi request reprint Brain ouabain stimulates peripheral marinobufagenin via angiotensin II signalling in NaCl-loaded Dahl-S rats
    Olga V Fedorova
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Hypertens 23:1515-23. 2005
    ..In hypertensive DS rats, EO raises blood pressure (BP) via an ATII-sensitive pathway. We hypothesized that an NaCl-induced increase in MBG is linked to the EO-stimulated ATII pathway...
  81. pmc The burden of obesity on blood pressure is reduced in older persons: the SardiNIA study
    M I Pikilidou
    Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute of Aging, Baltimore, Maryland, USA
    Obesity (Silver Spring) 21:E10-3. 2013
    ..Being overweight or obese increases the risk of elevated blood pressure. However differences of their effects on blood pressure in different age groups are not clear...
  82. pmc Intracellular signaling pathways required for rat vascular smooth muscle cell migration. Interactions between basic fibroblast growth factor and platelet-derived growth factor
    C Bilato
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Clin Invest 96:1905-15. 1995
    ..These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration...
  83. ncbi request reprint The old heart: operating on the edge
    E G Lakatta
    National Institute on Aging, Gerontology Research Center, Laboratory of Cardiovascular Science, Baltimore, MD 21224-6825, USA
    Novartis Found Symp 235:172-96; discussion 196-201, 217-20. 2001
    ..The risk of excess Ca2+ loading within the senescent heart can potentially be reduced by gene therapy to restore Ca2+ regulatory proteins, by diet to reverse the membrane omega 6:omega 3 PUFA imbalance, or by antioxidants...
  84. ncbi request reprint Functional correlates of central arterial geometric phenotypes
    A Scuteri
    Gerontology Research Center, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Hypertension 38:1471-5. 2001
    ..The interplay among these factors, particularly circumferential wall and FSS, likely determines the CGP; conversely, the resultant CGP may modulate the FSS and wall stress for a given pressure and flow...
  85. ncbi request reprint Catecholamines and cardiovascular function in aging
    E G Lakatta
    Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland
    Endocrinol Metab Clin North Am 16:877-91. 1987
    ....
  86. ncbi request reprint High-density lipoprotein cholesterol and vascular stiffness at baseline in the activity counseling trial
    R J Havlik
    Epidemiology, Demography, and Biometry Program, National Institute on Aging, Bethesda, Maryland 20892 9205, USA
    Am J Cardiol 87:104-7, A9. 2001
    ..High-density lipoprotein cholesterol may be an indirect indicator of aerobic capacity or of less atherosclerosis, suggesting mechanisms for preserving vascular integrity...
  87. ncbi request reprint Enhanced G(i) signaling selectively negates beta2-adrenergic receptor (AR)--but not beta1-AR-mediated positive inotropic effect in myocytes from failing rat hearts
    Rui Ping Xiao
    The Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
    Circulation 108:1633-9. 2003
    ....
  88. pmc Increased aortic calpain-1 activity mediates age-associated angiotensin II signaling of vascular smooth muscle cells
    Liqun Jiang
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, United States of America
    PLoS ONE 3:e2231. 2008
    ..The consequences of engagement of calpain-1 with its substrates, however, in governing the age-associated proinflammatory status within the arterial wall, remains unknown...
  89. ncbi request reprint Prevalence of specific variant carotid geometric patterns and incidence of cardiovascular events in older persons. The Cardiovascular Health Study (CHS E-131)
    Angelo Scuteri
    Laboratory of Cardiovascular Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    J Am Coll Cardiol 43:187-93. 2004
    ..We hypothesized that variant geometric patterns of the common carotid artery (CCA) predict the incidence of cardiovascular disease (CVD), after accounting for CCA intima-medial thickness (IMT)...
  90. ncbi request reprint Adaptive mechanisms of intracellular calcium homeostasis in mammalian hibernators
    Shi Qiang Wang
    National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China
    J Exp Biol 205:2957-62. 2002
    ..Understanding the adaptive mechanisms of Ca(2+) regulation in hibernating mammals may suggest new strategies to protect nonhibernator cells, including those of humans, from Ca(2+)-induced dysfunction...
  91. ncbi request reprint The metabolic syndrome in older individuals: prevalence and prediction of cardiovascular events: the Cardiovascular Health Study
    Angelo Scuteri
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, 5600 Nathan Shock Dr, Baltimore, MD 21224, USA
    Diabetes Care 28:882-7. 2005
    ..We also compared the prognostic significance of the two definitions of the metabolic syndrome...
  92. doi request reprint Constitutive phosphodiesterase activity restricts spontaneous beating rate of cardiac pacemaker cells by suppressing local Ca2+ releases
    Tatiana M Vinogradova
    Laboratory of Cardiovascular Science, Gerontology Research Center, NIA, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 6825, USA
    Circ Res 102:761-9. 2008
    ....
  93. ncbi request reprint Relationship between androgenic hormones and arterial stiffness, based on longitudinal hormone measurements
    Hidetaka Hougaku
    Clinical Research Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21225, USA
    Am J Physiol Endocrinol Metab 290:E234-42. 2006
    ..05). Thus the adverse influence of low T on the cardiovascular system in men may be mediated in part via the effects of T on vascular structure and function...
  94. ncbi request reprint Nitric oxide inhibition as a mechanism for blood pressure increase during salt loading in normotensive postmenopausal women
    Angelo Scuteri
    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, Maryland, USA
    J Hypertens 21:1339-46. 2003
    ..We determined whether changes in endothelium-dependent vasodilation (EDD) and plasma ADMA predict changes in blood pressure (BP) after salt loading in normotensive postmenopausal women (PMW)...
  95. ncbi request reprint Discovering altered genomic expression patterns in heart: transcriptome determination by serial analysis of gene expression
    S V Anisimov
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA
    Eur J Heart Fail 3:271-81. 2001
    ....
  96. ncbi request reprint Minoxidil inhibits proliferation and migration of cultured vascular smooth muscle cells and neointimal formation after balloon catheter injury
    Z Li
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA
    J Cardiovasc Pharmacol 36:270-6. 2000
    ..Data demonstrate that minoxidil inhibits vascular SMC proliferation and migration both in vitro and in vivo, and therefore may be useful to inhibit SMC hyperplasia that occurs in restenosis and other vascular diseases...
  97. ncbi request reprint Is the apoE4 allele an independent predictor of coronary events?
    A Scuteri
    Laboratory of Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224, USA
    Am J Med 110:28-32. 2001
    ..Although the apolipoprotein E genotype epsilon4 (apoE4) has been associated with high cholesterol levels, whether it is an independent predictor of coronary events is not certain...
  98. pmc Early contribution of arterial wave reflection to left ventricular relaxation abnormalities in a community-dwelling population of normotensive and untreated hypertensive men and women
    M Canepa
    1 Laboratory of Cardiovascular Sciences, Human Cardiovascular Studies Unit, National Institute on Aging, NIH, Baltimore, MD, USA 2 Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, NIH, Baltimore, MD, USA 3 Division of Cardiology, Research Center of Cardiovascular Biology, University of Genova, Genova, Italy
    J Hum Hypertens 28:85-91. 2014
    ....
  99. ncbi request reprint Endogenous Na/K-ATPase inhibitors in patients with preeclampsia
    I V Averina
    Laboratory of Cardiovascular Science, National Institute on Aging, NIH, Baltimore, MD 21224, USA
    Cell Mol Biol (Noisy-le-grand) 52:19-23. 2006
    ..25 +/- 0.25 micromol Pi/ml/hr, P>0.5). The present observations provide evidence for a role for MBG in the pathogenesis of PE, and suggest that antibodies against MBG may be useful in the treatment of this syndrome...
  100. ncbi request reprint Paclitaxel stent coating inhibits neointimal hyperplasia at 4 weeks in a porcine model of coronary restenosis
    A W Heldman
    Division of Cardiology, Department of Pathology, Johns Hopkins School of Medicine, Baltimore, MD, USA
    Circulation 103:2289-95. 2001
    ..We tested whether paclitaxel-coated coronary stents are effective at preventing neointimal proliferation in a porcine model of restenosis...
  101. ncbi request reprint Continuum of cardiovascular performance across a broad range of fitness levels in healthy older men
    S P Schulman
    Gerontology Research Center, University of Maryland School of Medicine and Geriatrics Research, Baltimore, USA
    Circulation 94:359-67. 1996
    ....