HORMONAL REGULATION OF BLOOD PRESSURE

Summary

Principal Investigator: Michal Laniado Schwartzman
Abstract: DESCRIPTION (provided by applicant): The objective of this Program Project Grant continues to concentrate on the role of the cytochrome P450 (CYP)-derived eicosanoids in the regulation of renal and vascular function and in the control of blood pressure. This Program provided paradigms and scientific leads for a framework of CYP-eicosanoid research in the field of hypertension. The relevance ofthis research to human health is highlighted in recent studies by Program investigators and others demonstrating the molecular and functional association between CYP-eicosanolds and cardiovascular disease including diabetes, stroke and hypertension. This proposal builds on this foundation and brings novel concepts and new directions to this area of research. It incorporates the vascular and renal mechanisms and the inflammatory component of hypertension in terms of interactions between the CYP-derived eicosanoids, EETs and 20-HETE, and two distinct regulatory circuits, the renin-angiotensin system (RAS) and the heme oxygenases (HO). This theme is depicted in three projects. Project 1 focuses on the interactions between the CYP4A-derived 20-HETE and the renin angiotensin system and investigate the role of endothelial ACE in 20-HETE-mediated vascular dysfunction and hypertension. Project 2 examines the role of K+ intake and angiotensin II in regulating the inhibitory effect of CYP2C44-dependent EETs on sodium transport (epithelial Na+ channel) in the cortical collecting duct and its impact on hypertension. Project 3 determines the molecular mechanisms by which an interplay between HO-1 and EETs modulates adipocyte function and adiponectin levels to prevent the development of vascular dysfunction in obesity-induced hypertension. These projects will be supported by three Cores: Core A provides administrative support. Core B provides LC-MS/MS-based measurements of eicosanoids. Core C provides molecular, genotypic and phenotypic support for animal research. This Program Project combines interdisciplinary approach to explore the integrative biology of EETs and HETEs, key modulators of renal salt handling, vascular endothelial integrity and vascular tone, in the pathophysiology of hypertension and cardiovascular disease. The objective of this Program Project Grant continues to concentrate on the role of the cytochrome P450 (CYP)-derived eicosanoids in the regulation of renal and vascular function and in the control of blood pressure. This Program provided paradigms and scientific leads for a framework of CYP-eicosanoid research in the field of hypertension. The relevance ofthis research to human health is highlighted in recent studies by Program investigators and others demonstrating the molecular and functional association between CYP-eicosanolds and cardiovascular disease including diabetes, stroke and hypertension. This proposal builds on this foundation and brings novel concepts and new directions to this area of research. It incorporates the vascular and renal mechanisms and the inflammatory component of hypertension in terms of interactions between the CYP-derived eicosanoids, EETs and 20-HETE, and two distinct regulatory circuits, the renin-angiotensin system (RAS) and the heme oxygenases (HO). This theme is depicted in three projects. Project 1 focuses on the interactions between the CYP4A-derived 20-HETE and the renin angiotensin system and investigate the role of endothelial ACE in 20-HETE-mediated vascular dysfunction and hypertension. Project 2 examines the role of K+ intake and angiotensin II in regulating the inhibitory effect of CYP2C44-dependent EETs on sodium transport (epithelial Na+ channel) in the cortical collecting duct and its impact on hypertension. Project 3 determines the molecular mechanisms by which an interplay between HO-1 and EETs modulates adipocyte function and adiponectin levels to prevent the development of vascular dysfunction in obesity-induced hypertension. These projects will be supported by three Cores: Core A provides administrative support. Core B provides LC-MS/MS-based measurements of eicosanoids. Core C provides molecular, genotypic and phenotypic support for animal research. This Program Project combines interdisciplinary approach to explore the integrative biology of EETs and HETEs, key modulators of renal salt handling, vascular endothelial integrity and vascular tone, in the pathophysiology of hypertension and cardiovascular disease. ular tone, in the pathophysiology of hypertension and cardiovascular disease.
Funding Period: 1997-09-01 - 2016-03-31
more information: NIH RePORT

Top Publications

  1. pmc Heme oxygenase-1 induction modulates hypoxic pulmonary vasoconstriction through upregulation of ecSOD
    Mansoor Ahmad
    Departments of Physiology, New York Medical College, Valhalla, New York 10595, USA
    Am J Physiol Heart Circ Physiol 297:H1453-61. 2009
  2. pmc TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion
    Chun Cheng Andy Chen
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 299:F1141-50. 2010
  3. pmc Lentiviral-human heme oxygenase targeting endothelium improved vascular function in angiotensin II animal model of hypertension
    Jian Cao
    Department of Physiology and Pharmacology, The University of Toledo, Toledo, OH 43614, USA
    Hum Gene Ther 22:271-82. 2011
  4. pmc CYP4A2-induced hypertension is 20-hydroxyeicosatetraenoic acid- and angiotensin II-dependent
    Komal Sodhi
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Hypertension 56:871-8. 2010
  5. ncbi Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation
    Ming Li
    Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka 570 8506, Japan
    J Autoimmun 35:414-23. 2010
  6. pmc Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice
    Angela Burgess
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
    Hypertension 56:1124-30. 2010
  7. pmc Stimulation of A(₂a) adenosine receptor abolishes the inhibitory effect of arachidonic acid on the basolateral 50-pS K channel in the thick ascending limb
    Mingxiao Wang
    Dept of Pharmacology, Harbin Med Univ, Harbin 150086, China
    Am J Physiol Renal Physiol 300:F906-13. 2011
  8. pmc Differential regulation of NFAT5 by NKCC2 isoforms in medullary thick ascending limb (mTAL) cells
    Shoujin Hao
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Am J Physiol Renal Physiol 300:F966-75. 2011
  9. pmc Androgen-dependent hypertension is mediated by 20-hydroxy-5,8,11,14-eicosatetraenoic acid-induced vascular dysfunction: role of inhibitor of kappaB Kinase
    Cheng Chia Wu
    New York Medical College, Department of Pharmacology, 15 Dana Road, Valhalla, NY 10595, USA
    Hypertension 57:788-94. 2011
  10. pmc Apolipoprotein A-I mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice
    C Vecoli
    Scuola Superiore Sant Anna, Pisa, Italy
    J Cell Biochem 112:2616-26. 2011

Research Grants

Detail Information

Publications123 found, 100 shown here

  1. pmc Heme oxygenase-1 induction modulates hypoxic pulmonary vasoconstriction through upregulation of ecSOD
    Mansoor Ahmad
    Departments of Physiology, New York Medical College, Valhalla, New York 10595, USA
    Am J Physiol Heart Circ Physiol 297:H1453-61. 2009
    ..Therefore, HO-1 induction in BPA increases ecSOD expression associated with enhanced generation of peroxide in amounts that may not be adequately removed during hypoxia, leading to an attenuation of HPV...
  2. pmc TNFR1-deficient mice display altered blood pressure and renal responses to ANG II infusion
    Chun Cheng Andy Chen
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 299:F1141-50. 2010
    ..These findings indicate deletion of TNFR1 is associated with an exacerbated SBP response, decrease in HR, and altered renal function in ANG II-dependent hypertension...
  3. pmc Lentiviral-human heme oxygenase targeting endothelium improved vascular function in angiotensin II animal model of hypertension
    Jian Cao
    Department of Physiology and Pharmacology, The University of Toledo, Toledo, OH 43614, USA
    Hum Gene Ther 22:271-82. 2011
    ....
  4. pmc CYP4A2-induced hypertension is 20-hydroxyeicosatetraenoic acid- and angiotensin II-dependent
    Komal Sodhi
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Hypertension 56:871-8. 2010
    ....
  5. ncbi Successful modulation of type 2 diabetes in db/db mice with intra-bone marrow--bone marrow transplantation plus concurrent thymic transplantation
    Ming Li
    Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka 570 8506, Japan
    J Autoimmun 35:414-23. 2010
    ..Our data show that IBM-BMT + TT treatment normalizes T cell subsets, cytokine imbalance and insulin sensitivity in the db/db mouse, suggesting that IBM-BMT + TT is a viable therapeutic option in the treatment of T2 DM...
  6. pmc Adipocyte heme oxygenase-1 induction attenuates metabolic syndrome in both male and female obese mice
    Angela Burgess
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
    Hypertension 56:1124-30. 2010
    ..These findings offer the possibility of treating not only hypertension, but also other detrimental metabolic consequences of obesity including insulin resistance and dyslipidemia in obese populations by induction of HO-1 in adipocytes...
  7. pmc Stimulation of A(₂a) adenosine receptor abolishes the inhibitory effect of arachidonic acid on the basolateral 50-pS K channel in the thick ascending limb
    Mingxiao Wang
    Dept of Pharmacology, Harbin Med Univ, Harbin 150086, China
    Am J Physiol Renal Physiol 300:F906-13. 2011
    ..We conclude that stimulation of adenosine A(₂a) receptor increased the 50-pS K channel activity in the TAL, an effect that is achieved by suppression of PLA₂ activity and 20-HETE-induced inhibition...
  8. pmc Differential regulation of NFAT5 by NKCC2 isoforms in medullary thick ascending limb (mTAL) cells
    Shoujin Hao
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Am J Physiol Renal Physiol 300:F966-75. 2011
    ..These findings suggest that NKCC2A and NKCC2F exhibit differential effects on NFAT5 expression and transcriptional activity in response to hypertonicity produced by high NaCl concentration...
  9. pmc Androgen-dependent hypertension is mediated by 20-hydroxy-5,8,11,14-eicosatetraenoic acid-induced vascular dysfunction: role of inhibitor of kappaB Kinase
    Cheng Chia Wu
    New York Medical College, Department of Pharmacology, 15 Dana Road, Valhalla, NY 10595, USA
    Hypertension 57:788-94. 2011
    ..These findings suggest that inhibition of IKK attenuates the androgen-dependent 20-HETE-mediated increase in blood pressure by inhibiting both 20-HETE-dependent endothelial activation and dysfunction...
  10. pmc Apolipoprotein A-I mimetic peptide L-4F prevents myocardial and coronary dysfunction in diabetic mice
    C Vecoli
    Scuola Superiore Sant Anna, Pisa, Italy
    J Cell Biochem 112:2616-26. 2011
    ..These effects were associated with stimulation of HO-1 resulting in increased levels of anti-inflammatory, anti-oxidative, and vasodilatatory action through a mechanism involving increased levels of adiponectin, pAMPK, and peNOS...
  11. pmc The role of 20-HETE in androgen-mediated hypertension
    Cheng Chia Wu
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA chengchia
    Prostaglandins Other Lipid Mediat 96:45-53. 2011
    ..In this review, we will discuss the pro-hypertensive effects of 20-HETE and its role in androgen-induced vascular dysfunction and hypertension...
  12. pmc Crosstalk between EET and HO-1 downregulates Bach1 and adipogenic marker expression in mesenchymal stem cell derived adipocytes
    Luca Vanella
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
    Prostaglandins Other Lipid Mediat 96:54-62. 2011
    ..In summary, EET agonist treatment inhibits adipogenesis and decreases the levels of inflammatory cytokines suggesting the potential action of EETs as intracellular lipid signaling modulators of adipogenesis and adiponectin...
  13. pmc Eicosanoids and tumor necrosis factor-alpha in the kidney
    Nicholas R Ferreri
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Prostaglandins Other Lipid Mediat 98:101-6. 2012
    ..The molecular mechanism for these effects likely includes inhibition of Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2) expression and trafficking...
  14. pmc Resolution, the grail for healthy ocular inflammation
    Karsten Gronert
    Vision Science Program, School of Optometry, University of California, 594 Minor Hall, MC 2020, Berkeley, CA 94720, USA
    Exp Eye Res 91:478-85. 2010
    ....
  15. ncbi Red blood cells (RBCs), epoxyeicosatrienoic acids (EETs) and adenosine triphosphate (ATP)
    Houli Jiang
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Pharmacol Rep 62:468-74. 2010
    ..The function and pathophysiological roles of trans-EETs and erythro-DHETs has yet to be integrated into a physiological and pathophysiological context...
  16. pmc Endothelial-specific CYP4A2 overexpression leads to renal injury and hypertension via increased production of 20-HETE
    Kazuyoshi Inoue
    Dept of Pharmacology, New York Medical College, Valhalla, NY, USA
    Am J Physiol Renal Physiol 297:F875-84. 2009
    ....
  17. pmc Epoxyeicosatrienoic acid agonist rescues the metabolic syndrome phenotype of HO-2-null mice
    Komal Sodhi
    Department of Pharmacology New York Medical College, Valhalla, New York, USA
    J Pharmacol Exp Ther 331:906-16. 2009
    ..A deficiency in one of these protective systems may contribute to the adverse manifestations associated with the clinical progression of the metabolic syndrome...
  18. pmc Dual pathways of carbon monoxide-mediated vasoregulation: modulation by redox mechanisms
    Brian D Lamon
    Department of Pharmacology, New York Medical College, Valhalla, NY, USA
    Circ Res 105:775-83. 2009
    ..CO has been shown to function as both a vasoconstrictor and vasodilator; however, factors that dictate the vasoregulatory phenotype of this gas are unknown...
  19. pmc Heme oxygenase-2 deletion causes endothelial cell activation marked by oxidative stress, inflammation, and angiogenesis
    Lars Bellner
    Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
    J Pharmacol Exp Ther 331:925-32. 2009
    ..This transformation underscores the importance of HO-2 in the regulation of endothelial cell homeostasis...
  20. pmc 20-hydroxy-5,8,11,14-eicosatetraenoic acid mediates endothelial dysfunction via IkappaB kinase-dependent endothelial nitric-oxide synthase uncoupling
    Jennifer Cheng
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Pharmacol Exp Ther 332:57-65. 2010
    ..The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation...
  21. pmc HO-1 expression increases mesenchymal stem cell-derived osteoblasts but decreases adipocyte lineage
    Luca Vanella
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, USA
    Bone 46:236-43. 2010
    ..Thus, targeting HO-1 expression is a portal to increased osteoblast stem cell differentiation and to the attenuation of osteoporosis by the promotion of bone formation...
  22. pmc Overexpression of heme oxygenase-1 increases human osteoblast stem cell differentiation
    Ignazio Barbagallo
    Department of Biological Chemistry, Medical Chemistry and Molecular Biology, University of Catania, Catania, Italy
    J Bone Miner Metab 28:276-88. 2010
    ..Thus, the targeting of HO-1 gene expression presents a portal to increase osteoblast function and differentiation and attenuate osteoporosis by promoting bone formation...
  23. pmc Molecular cloning and enzymatic characterization of sheep CYP2J
    A Messina
    Istituto di Fisiologia Clinica, Consiglio Nazionale delle Ricerche, Via Moruzzi 1, Pisa, Italy
    Xenobiotica 40:109-18. 2010
    ....
  24. pmc Improved myocardial perfusion in chronic diabetic mice by the up-regulation of pLKB1 and AMPK signaling
    Claudia Kusmic
    CNR Institute of Clinical Physiology, Pisa, Italy
    J Cell Biochem 109:1033-44. 2010
    ..The restoration of microvascular function suggests a new therapeutic approach to even advanced cardiac microvascular derangement in diabetes...
  25. pmc Epoxyeicosatrienoic acid agonist regulates human mesenchymal stem cell-derived adipocytes through activation of HO-1-pAKT signaling and a decrease in PPARγ
    Dong Hyun Kim
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA
    Stem Cells Dev 19:1863-73. 2010
    ..These novel observations highlight the seminal role of arachidonic acid metabolism in MSCs and suggest that an EET agonist may have potential therapeutic use in the treatment of dyslipidemia, diabetes, and the metabolic syndrome...
  26. pmc Profile of lipid and protein autacoids in diabetic vitreous correlates with the progression of diabetic retinopathy
    Michal Laniado Schwartzman
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Diabetes 59:1780-8. 2010
    ..This study was aimed at obtaining a profile of lipids and proteins with a paracrine function in normal and diabetic vitreous and exploring whether the profile correlates with retinal pathology...
  27. pmc High potassium intake enhances the inhibitory effect of 11,12-EET on ENaC
    Peng Sun
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Am Soc Nephrol 21:1667-77. 2010
    ..In conclusion, high dietary potassium enhances the inhibitory effect of AA and 11,12-EET on ENaC by increasing CYP epoxygenase activity and decreasing sEH activity, respectively...
  28. ncbi Regulation and function of potassium channels in aldosterone-sensitive distal nephron
    Wen Hui Wang
    Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
    Curr Opin Nephrol Hypertens 19:463-70. 2010
    ..The aim of the review is to provide an overview of the recent development regarding physiological function of the K channels and the novel factors which modulate the K channels of the ASDN...
  29. ncbi The red blood cell participates in regulation of the circulation by producing and releasing epoxyeicosatrienoic acids
    Houli Jiang
    Department of Pharmacology, New York Medical College, Valhalla, NY, USA
    Prostaglandins Other Lipid Mediat 98:91-3. 2012
    ..We predict that trans-EETs and cis-EETs will occupy important therapeutic roles in a broad spectrum of diseases and abnormal physiological conditions such as that resulting from high salt intake and hypertension...
  30. pmc Cyp2c44 epoxygenase is essential for preventing the renal sodium absorption during increasing dietary potassium intake
    Peng Sun
    Department of Pharmacology, New York Medical College, 15 Dana Rd, Valhalla, NY 10595, USA
    Hypertension 59:339-47. 2012
    ....
  31. ncbi High-fat diet exacerbates renal dysfunction in SHR: reversal by induction of HO-1-adiponectin axis
    Jian Cao
    First Geriatric Cardiology Department, Chinese PLA General Hospital, Beijing, China
    Obesity (Silver Spring) 20:945-53. 2012
    ..Taken together, our results demonstrate that high-fat diet induces a metabolic syndrome-like phenotype in hypertensive rats, which is amenable to rescue by increases in HO-1- and adiponectin-dependent pathways...
  32. pmc Role of cytochrome P450 epoxygenase in regulating renal membrane transport and hypertension
    Jorge Capdevila
    Department of Medicine, Vanderbilt University, Nashville, Tennessee, USA
    Curr Opin Nephrol Hypertens 22:163-9. 2013
    ..This review summarizes and updates recent progress in this area of research...
  33. ncbi Heme oxygenase-2/adiponectin protein-protein interaction in metabolic syndrome
    Luca Vanella
    Biochemistry Section, Department of Drug Sciences, University of Catania, I 95125 Catania, Italy
    Biochem Biophys Res Commun 432:606-11. 2013
    ..Thus, crosstalk between HO-2 and HO-1 could be manipulated in a therapeutic approach to ameliorate the deleterious effects of obesity and the metabolic syndrome...
  34. pmc Angiotensin II stimulates basolateral 10-pS Cl channels in the thick ascending limb
    Peng Wu
    Department of Pharmacology, New York Medical College, 15 Dana Rd, Valhalla, NY 10595, USA
    Hypertension 61:1211-7. 2013
    ..The stimulatory effect of AngII on the basolateral Cl channel may contribute to AngII-induced increases in NaCl reabsorption in the TAL and AngII-infuse-induced hypertension...
  35. pmc Androgen-sensitive hypertension associates with upregulated vascular CYP4A12-20-HETE synthase
    Cheng Chia Wu
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Am Soc Nephrol 24:1288-96. 2013
    ..Taken together, these results suggest that 20-HETE both mediates androgen-induced hypertension and can cause hypertension independent of androgen. ..
  36. pmc HO-1 induction improves the type-1 cardiorenal syndrome in mice with impaired angiotensin II-induced lymphocyte activation
    Sumit R Monu
    Department of Medicine, Joan C Edwards School of Medicine, Marshall University, Huntington, WV 25701 3655, USA
    Hypertension 62:310-6. 2013
    ..The study demonstrates that T-lymphocyte suppression facilitated the HO-1-dependent improvement in the attenuation of type-1 cardiorenal syndrome. ..
  37. pmc PPARδ binding to heme oxygenase 1 promoter prevents angiotensin II-induced adipocyte dysfunction in Goldblatt hypertensive rats
    K Sodhi
    Department of Medicine, Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
    Int J Obes (Lond) 38:456-65. 2014
    ....
  38. pmc Dysregulated heme oxygenase-ferritin system in pterygium pathogenesis
    Timothy Fox
    Department of Pharmacology, New York Medical College, Valhalla, NY, USA
    Cornea 32:1276-82. 2013
    ..These eicosanoids are subjected to regulation by enzymes, such as heme oxygenases (HOs) and ferritin...
  39. pmc 20-HETE induces remodeling of renal resistance arteries independent of blood pressure elevation in hypertension
    Yan Ding
    1Department of Pharmacology, New York Medical College, 15 Dana Road, BSB Rm 530, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 305:F753-63. 2013
    ..This study demonstrated that 20-HETE is a key regulator of microvascular remodeling in hypertension; its effect is independent of blood pressure elevation and androgen levels. ..
  40. pmc Increased HO-1 levels ameliorate fatty liver development through a reduction of heme and recruitment of FGF21
    Terry D Hinds
    Department of Medicine, Joan C Edwards School of Medicine, Marshall University, Huntington, West Virginia, USA
    Obesity (Silver Spring) 22:705-12. 2014
    ..Obese leptin deficient (ob/ob) mice are a model of adiposity that displays increased levels of fat, glucose, and liver lipids. Our hypothesis is that HO-1 overexpression ameliorates fatty liver development...
  41. pmc The Cyp2c44 epoxygenase regulates epithelial sodium channel activity and the blood pressure responses to increased dietary salt
    Jorge H Capdevila
    From the Department of Medicine, Vanderbilt University, Nashville Tennessee 37232
    J Biol Chem 289:4377-86. 2014
    ..It is expected that these results will serve as a basis for the development of novel strategies for the early diagnosis and treatment of hypertension and of pathophysiologies associated with dysfunctional mitogenic signaling. ..
  42. pmc NFAT5 is protective against ischemic acute kidney injury
    Shoujin Hao
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595
    Hypertension 63:e46-52. 2014
    ..Collectively, the data suggest that NFAT5 is part of a protective mechanism that limits renal damage induced by IRI. ..
  43. pmc 20-HETE regulates the angiogenic functions of human endothelial progenitor cells and contributes to angiogenesis in vivo
    Li Chen
    Department of Pharmacology, School of Medicine, Wuhan University, Wuhan, PR China L C, J Y, A M G Department of Pharmacology, New York Medical College, Valhalla, New York L C, R A, M S, K H G, M L S, A M G Department of Obstetrics and Gynecology, Westchester Medical Center, Valhalla, New York M K Obstetrics and Gynecology, Phelps Memorial Hospital Center, Sleepy Hollow, New York L G M University of Texas Southwestern Medical Center, Dallas, Texas J R F and Henry Ford Hospital, Detroit, Michigan A S A, A G S
    J Pharmacol Exp Ther 348:442-51. 2014
    ..These results strengthened the notion that 20-HETE regulates the angiogenic functions of EPC in vitro and EPC-mediated angiogenesis in vivo...
  44. pmc Soluble epoxide hydrolase-dependent regulation of myogenic response and blood pressure
    Dong Sun
    Department of Physiology, New York Medical College, Valhalla, New York
    Am J Physiol Heart Circ Physiol 306:H1146-53. 2014
    ..In conclusion, the increased EET bioavailability, as a function of deficiency/inhibition of sEH, potentiates vasodilator responses that counteract pressure-induced vasoconstriction to lower blood pressure...
  45. pmc Cyclooxygenase-2 dependent metabolism of 20-HETE increases adiposity and adipocyte enlargement in mesenchymal stem cell-derived adipocytes
    Dong Hyun Kim
    Joan C Edwards School of Medicine, Marshall University, Huntington, WV, USA
    J Lipid Res 54:786-93. 2013
    ..Taken together we show for the first time that 20-HETE-derived COX-2-dependent 20-OH-PGE₂ enhances mature inflamed adipocyte hypertrophy in MSC undergoing adipogenic differentiation...
  46. pmc Epoxyeicosatrienoic acids (EETs) regulate epithelial sodium channel activity by extracellular signal-regulated kinase 1/2 (ERK1/2)-mediated phosphorylation
    Nataliya Pidkovka
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Biol Chem 288:5223-31. 2013
    ....
  47. pmc EET agonist prevents adiposity and vascular dysfunction in rats fed a high fat diet via a decrease in Bach 1 and an increase in HO-1 levels
    Komal Sodhi
    Department of Physiology and Pharmacology, The University of Toledo College of Medicine, Health Education Building, 3000 Arlington Avenue, Toledo, OH 43614 2598, USA
    Prostaglandins Other Lipid Mediat 98:133-42. 2012
    ..Taken together, our findings suggest that the EETs stimulate HO-1 expression via suppression of Bach 1 and interplay of these two systems affords vascular and metabolic protection in diet induced obesity...
  48. pmc Heme induced oxidative stress attenuates sirtuin1 and enhances adipogenesis in mesenchymal stem cells and mouse pre-adipocytes
    Nitin Puri
    Department of Physiology and Pharmacology, College of Medicine, The University of Toledo, Toledo, Ohio 43614, USA
    J Cell Biochem 113:1926-35. 2012
    ..Anti-oxidant induced offsetting of these effects of heme supports the role of heme-dependent oxidative stress in mediating such events...
  49. pmc ApoA1: mimetic peptide reverses adipocyte dysfunction in vivo and in vitro via an increase in heme oxygenase (HO-1) and Wnt10b
    Luca Vanella
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH, USA
    Cell Cycle 11:706-14. 2012
    ..These findings support the hypothesis that L-4F increases early adipocyte markers, HO-1-adiponectin, WNT10b and decreases Peg1/Mest, negative regulators of adipocyte differentiation...
  50. pmc Heme oxygenase (HO-1) rescue of adipocyte dysfunction in HO-2 deficient mice via recruitment of epoxyeicosatrienoic acids (EETs) and adiponectin
    Angela P H Burgess
    Department of Physiology and Pharmacology, University of Toledo, Toledo, USA
    Cell Physiol Biochem 29:99-110. 2012
    ..Our aim was to examine the consequences of HO deficiency on MSC-derived adipogenesis in vitro using MSC derived from HO-2 null and WT mice in vivo...
  51. pmc Induction of angiotensin-converting enzyme and activation of the renin-angiotensin system contribute to 20-hydroxyeicosatetraenoic acid-mediated endothelial dysfunction
    Jennifer Cheng
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Arterioscler Thromb Vasc Biol 32:1917-24. 2012
    ....
  52. pmc Heme oxygenase gene targeting to adipocytes attenuates adiposity and vascular dysfunction in mice fed a high-fat diet
    Jian Cao
    Department of Geriatric Cardiology, Chinese PLA General Hospital Beijing, China
    Hypertension 60:467-75. 2012
    ..These effects are reversed by the HO activity inhibitor, stannous mesoporphyrin...
  53. pmc Tumor necrosis factor-alpha induces renal cyclooxygenase-2 expression in response to hypercalcemia
    Sailaja Battula
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, United States
    Prostaglandins Other Lipid Mediat 99:45-50. 2012
    ..This study demonstrates that COX-2 expression in the OM, secondary to hypercalemia, is TNF-dependent...
  54. pmc Antioxidants condition pleiotropic vascular responses to exogenous H(2)O(2): role of modulation of vascular TP receptors and the heme oxygenase system
    Nitin Puri
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Antioxid Redox Signal 18:471-80. 2013
    ..Where both dilation and constriction have been reported, we examined the hypothesis that the ability of H(2)O(2) to effect vasoconstriction or dilation is conditioned by redox mechanisms and may be modulated by antioxidants...
  55. ncbi Peroxisome proliferator-activated receptor delta agonist attenuates nicotine suppression effect on human mesenchymal stem cell-derived osteogenesis and involves increased expression of heme oxygenase-1
    Dong Hyun Kim
    Department of Physiology and Pharmacology, University of Toledo College of Medicine, Toledo, OH 43614, USA
    J Bone Miner Metab 31:44-52. 2013
    ..This offers insight into both how nicotine affects bone remodeling and a therapeutic approach to prevent fracture and osteoporosis in smokers...
  56. pmc Stem cell transplantation increases antioxidant effects in diabetic mice
    Ming Li
    Department of Stem Cell Disorders, Kansai Medical University, Moriguchi City, Osaka, Japan
    Int J Biol Sci 8:1335-44. 2012
    ..Thus IBM-BMT+TT unregulated the expression of HO-1, peNOS and pAKT, while decreasing iNOS levels in the kidney of db/db mice. This was associated with an improvement in renal function...
  57. pmc Carbon monoxide stimulates Ca2+ -dependent big-conductance K channels in the cortical collecting duct
    Zhijian Wang
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 304:F543-52. 2013
    ..We conclude that CO activates the BK channels, at least partially, through a NO-cGMP-independent pathway and that HO plays a role in mediating the effect of HK intake on the BK channels in the CCD...
  58. pmc NKCC2A and NFAT5 regulate renal TNF production induced by hypertonic NaCl intake
    Shoujin Hao
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 304:F533-42. 2013
    ..Since NKCC2A expression is restricted to the TAL, NKCC2A-dependent activation of NFAT5 is part of a pathway by which the TAL produces TNF in response to hypertonic NaCl intake...
  59. pmc Heme oxygenase-1 induction improves cardiac function following myocardial ischemia by reducing oxidative stress
    Yossi Issan
    Cardiac Research Laboratory, Felsenstein Medical Research Institute, Tel Aviv University, Petah Tikva, Israel
    PLoS ONE 9:e92246. 2014
    ..We aimed to investigate the protection and the mechanisms of HO-1 induction in cardiomyocytes subjected to hypoxia and in diabetic mice subjected to LAD ligation...
  60. pmc CYP-omega-hydroxylation-dependent metabolites of arachidonic acid inhibit the basolateral 10 pS chloride channel in the rat thick ascending limb
    Rui Min Gu
    Department of Pharmacology, Harbin Medical University, China
    Kidney Int 76:849-56. 2009
    ..We conclude that arachidonic acid inhibits the 10 pS chloride channel in the basolateral membrane of the medullary thick ascending limb, an effect mediated by the CYP-omega-hydroxylation-dependent metabolite 20-HETE...
  61. ncbi Adenosine inhibits ENaC via cytochrome P-450 epoxygenase-dependent metabolites of arachidonic acid
    Yuan Wei
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 290:F1163-8. 2006
    ..We conclude that adenosine inhibits ENaC activity by stimulation of the A(1) adenosine receptor in the CCD and that the effect of adenosine is mediated by 11,12-EET...
  62. pmc Heme oxygenase-2 is a critical determinant for execution of an acute inflammatory and reparative response
    Francesca Seta
    Department of Pharmacology, New York Medical College, Grassland Reservation, Valhalla, NY 10595, USA
    Am J Pathol 169:1612-23. 2006
    ..Thus, HO-2 sets in place a basal tone of anti-inflammatory signals that may be a prerequisite for the ordered execution of an inflammatory and reparative response...
  63. ncbi Impact of silencing HO-2 on EC-SOD and the mitochondrial signaling pathway
    S Turkseven
    Department of Pharmacology, New York Medical College, Valhalla, NY, USA
    J Cell Biochem 100:815-23. 2007
    ..In addition, localization of HO-1 in the mitochondrial compartment plays a critical role in mitochondria-mediated apoptosis...
  64. ncbi 11,12-epoxyeicosatrienoic acid stimulates heme-oxygenase-1 in endothelial cells
    David Sacerdoti
    Department of Clinical and Experimental Medicine, Clinica Medica 5, University of Padova, Via Giustiniani 2, 35100 Padova, Italy
    Prostaglandins Other Lipid Mediat 82:155-61. 2007
    ..These findings identify a novel effect of EETs on endothelial HO-1 and indicate that the signaling pathway of EETs in endothelial cells is possibly via an increase in HO-1 expression and activity...
  65. ncbi Long-lasting expression of HO-1 delays progression of type I diabetes in NOD mice
    Ming Li
    First Department of Pathology, Kansai Medical University, Moriguchi, Osaka, Japan
    Cell Cycle 6:567-71. 2007
    ....
  66. ncbi Vascular prostaglandin synthesis: the early days
    J C McGiff
    Department of Pharmacology, New York Medical College, Vahalla, NY 10595, USA
    Pharmacol Rep 58:47-51. 2006
    ..These studies were responsible for opening the modern era of vascular biology that has facilitated the development of a rational approach to the treatment of diabetic and hypertensive complications involving the arterial circulation...
  67. ncbi Heme oxygenase -1 gene therapy: recent advances and therapeutic applications
    Nader G Abraham
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Curr Gene Ther 7:89-108. 2007
    ....
  68. ncbi Adenosine stimulates the basolateral 50 pS K channels in the thick ascending limb of the rat kidney
    Ruimin Gu
    Dept of Pharmacology, Harbin Medical University, Harbin 150086, China
    Am J Physiol Renal Physiol 293:F299-305. 2007
    ..We conclude that adenosine activates the 50 pS K channel in the basolateral membrane of the TAL and the stimulatory effect is mainly mediated by a PKA-dependent pathway via the A2 adenosine receptor in the TAL...
  69. ncbi Long-term treatment with the apolipoprotein A1 mimetic peptide increases antioxidants and vascular repair in type I diabetic rats
    Stephen J Peterson
    Department of Medicine, New York Medical College, Valhalla, NY 10595, USA
    J Pharmacol Exp Ther 322:514-20. 2007
    ....
  70. ncbi Interdiction of the diabetic state in NOD mice by sustained induction of heme oxygenase: possible role of carbon monoxide and bilirubin
    Ming Li
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Antioxid Redox Signal 9:855-63. 2007
    ....
  71. ncbi Metabolic syndrome: psychosocial, neuroendocrine, and classical risk factors in type 2 diabetes
    N G Abraham
    New York Medical College, Department of Pharmacology, Valhalla, NY 10595 USA
    Ann N Y Acad Sci 1113:256-75. 2007
    ..If this proves to be the case, then the scene will be set to develop glutathione peroxidase mimetics for use in preclinical and clinical trials...
  72. ncbi Induction of heme oxygenase-1 in renovascular hypertension is associated with inhibition of apoptosis
    F T Botros
    Department of Pharmacology, New York Medical College, Valhalla, New York 10595, USA
    Cell Mol Biol (Noisy-le-grand) 53:51-60. 2007
    ....
  73. pmc Role of gp91phox -containing NADPH oxidase in mediating the effect of K restriction on ROMK channels and renal K excretion
    Elisa Babilonia
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    J Am Soc Nephrol 18:2037-45. 2007
    ..It is concluded that superoxide anions play a key role in suppressing K secretion during K restriction and that NOXII is involved in mediating the effect of low K intake on renal K secretion and ROMK channel activity...
  74. ncbi Vascular cytochrome P450 4A expression and 20-hydroxyeicosatetraenoic acid synthesis contribute to endothelial dysfunction in androgen-induced hypertension
    Harpreet Singh
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Hypertension 50:123-9. 2007
    ..05). The results strongly implicate vascular cytochrome P450 4A-derived 20-hydroxyeicosatetraenoic acid in the development of androgen-induced endothelial dysfunction and hypertension...
  75. ncbi CD163-Mediated hemoglobin-heme uptake activates macrophage HO-1, providing an antiinflammatory function
    Nader G Abraham
    Circ Res 99:911-4. 2006
  76. ncbi Heme oxygenase-1 inhibition of Nox oxidase activation is a microvascular endothelial antioxidant effect of NO
    Michael S Wolin
    Hypertension 48:826-7. 2006
  77. pmc Regulation of ROMK (Kir1.1) channels: new mechanisms and aspects
    Wen Hui Wang
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 290:F14-9. 2006
    ..Finally, a recent study indicated that ROMK channels can be monoubiquitinated and monoubiquitination regulates the surface expression of ROMK channels...
  78. ncbi NFAT regulates calcium-sensing receptor-mediated TNF production
    Huda Ismail Abdullah
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 290:F1110-7. 2006
    ..Elucidating CaR-mediated signaling pathways that regulate TNF production in the mTAL will be crucial to understanding mechanisms that regulate extracellular fluid volume and salt balance...
  79. ncbi Chronic CO levels have [corrected] a beneficial effect on vascular relaxation in diabetes
    Marco Di Pascoli
    Department of Pharmacology, New York Medical College, Valhalla, NY, USA
    Biochem Biophys Res Commun 340:935-43. 2006
    ....
  80. ncbi Adenosine2A receptor vasodilation of rat preglomerular microvessels is mediated by EETs that activate the cAMP/PKA pathway
    Mairead A Carroll
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 291:F155-61. 2006
    ..Thus in rat PGMV activation of A2AR is coupled to EET release upstream of adenylyl cyclase activation and EETs stimulate mono-ADP-ribosyltransferase, resulting in Gsalpha protein activation...
  81. ncbi Heme oxygenase-2 deficiency contributes to diabetes-mediated increase in superoxide anion and renal dysfunction
    Alvin I Goodman
    New York Medical College, Department of Pharmacology, Grassland Road, Valhalla, NY 10595, USA
    J Am Soc Nephrol 17:1073-81. 2006
    ..These observations indicate that HO activity is essential in preserving renal function and morphology in STZ-induced diabetic mice probably via mitigation of concomitant oxidative stress...
  82. ncbi Endothelial dysfunction and hypertension in rats transduced with CYP4A2 adenovirus
    Ji Shi Wang
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Circ Res 98:962-9. 2006
    ....
  83. ncbi Heme oxygenase-1 enhances renal mitochondrial transport carriers and cytochrome C oxidase activity in experimental diabetes
    Maria Antonietta Di Noia
    Department of Pharmaco Biology, University of Bari, 70125 Bari, Italy
    J Biol Chem 281:15687-93. 2006
    ..These observations in experimental diabetes suggest that the cytoprotective mechanism of HO-1 against oxidative stress involves an increase in the levels of MCs and anti-apoptotic proteins as well as in cytochrome c oxidase activity...
  84. pmc Salt-sensitive hypertension is associated with dysfunctional Cyp4a10 gene and kidney epithelial sodium channel
    Kiyoshi Nakagawa
    Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
    J Clin Invest 116:1696-702. 2006
    ..It is expected that these results could lead to new strategies for the early diagnosis and clinical management of this devastating disease...
  85. ncbi Carbon monoxide and biliverdin prevent endothelial cell sloughing in rats with type I diabetes
    Luigi Rodella
    University of Texas Southwestern Medical Center, Dallas, USA
    Free Radic Biol Med 40:2198-205. 2006
    ....
  86. ncbi Rat mesenteric arterial dilator response to 11,12-epoxyeicosatrienoic acid is mediated by activating heme oxygenase
    David Sacerdoti
    Dept of Clinical and Experimental Medicine, Univ of Padova, Italy, Via Giustiniani 2, 35100 Padova, Italy
    Am J Physiol Heart Circ Physiol 291:H1999-2002. 2006
    ..We conclude that the rat mesenteric vasodilator action of 11,12-EET is mediated via an increase in HO activity and an activation of calcium-activated potassium channels...
  87. ncbi Low Na intake suppresses expression of CYP2C23 and arachidonic acid-induced inhibition of ENaC
    Peng Sun
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 291:F1192-200. 2006
    ..We conclude that low Na intake downregulates the activity and expression of CYP2C23 and attenuates the inhibitory effect of AA on Na transport...
  88. ncbi Genetic suppression of HO-1 exacerbates renal damage: reversed by an increase in the antiapoptotic signaling pathway
    Rafal Olszanecki
    Dept of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 292:F148-57. 2007
    ..These findings underscore the prominent role of HO-1 in counteracting apoptosis in this 2K1C renovascular hypertension model...
  89. ncbi Up-regulation of heme oxygenase provides vascular protection in an animal model of diabetes through its antioxidant and antiapoptotic effects
    Adam L Kruger
    Division of Cardiology, Department of Medicine, New York Medical College, Valhalla, New York 10595, USA
    J Pharmacol Exp Ther 319:1144-52. 2006
    ....
  90. ncbi Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins
    A I Goodman
    Department of Pharmacology, New York Medical College, Valhalla, New York, USA
    Kidney Int 72:945-53. 2007
    ..Our study suggests that increased levels of heme oxygenase-1 are protective against acute kidney injury due to radiocontrast exposure...
  91. ncbi Characterization of a long-term rat mTAL cell line
    Ben Eng
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 293:F1413-22. 2007
    ..This cell line will be used in studies that address biochemical, molecular, and physiological mechanisms in the mTAL...
  92. ncbi Targeting endothelial cells with heme oxygenase-1 gene using VE-cadherin promoter attenuates hyperglycemia-mediated cell injury and apoptosis
    Amit Asija
    Department of Medicine, New York Medical College, Valhalla, New York 10595, USA
    Antioxid Redox Signal 9:2065-74. 2007
    ..These results demonstrate that endothelial cell survival after oxidative stress injury may be enhanced by targeting HO-1 expression, thus blocking inflammation, apoptosis, and thereby attenuating cardiovascular risk factors...
  93. pmc PGE2 inhibits basolateral 50 pS potassium channels in the thick ascending limb of the rat kidney
    Ruimin Gu
    Department of Physiology, Harbin Medical University, Harbin, China
    Kidney Int 74:478-85. 2008
    ..These studies show that inhibition of basolateral 50 pS potassium channels by PGE(2) is mediated by protein kinase-C, which in turn stimulates mitogen-activated protein kinases in the thick ascending limb of the rat kidney...
  94. pmc Exacerbated corneal inflammation and neovascularization in the HO-2 null mice is ameliorated by biliverdin
    Lars Bellner
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Exp Eye Res 87:268-78. 2008
    ..Hence, pharmacological amplification of this system may constitute a novel therapeutic strategy for the treatment of corneal disorders associated with excessive inflammation and neovascularization...
  95. pmc Calcium-sensing receptor signaling pathways in medullary thick ascending limb cells mediate COX-2-derived PGE2 production: functional significance
    Huda Ismail Abdullah
    Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA
    Am J Physiol Renal Physiol 295:F1082-9. 2008
    ..Our findings identified signaling elements required for CaR-mediated TNF production that are integral components regulating mTAL function via a mechanism involving COX-2 expression and PGE2 production...
  96. pmc Gene targeting and heme oxygenase-1 expression in prevention of hypertension induced by angiotensin II
    Nader G Abraham
    Hypertension 52:618-20. 2008
  97. pmc Hydrogen peroxide stimulates the Ca(2+)-activated big-conductance K channels (BK) through cGMP signaling pathway in cultured human endothelial cells
    De Li Dong
    Department of Pharmacology, Harbin Medical University
    Cell Physiol Biochem 22:119-26. 2008
    ..We conclude that H(2)O(2) stimulates the Ca2(+) BK channels through NO/sGC/cGMP pathway in cultured human endothelial cells...
  98. pmc Regulation of potassium (K) handling in the renal collecting duct
    Wen Hui Wang
    Department of Pharmacology, New York Medical College, Valhalla, 10595, USA
    Pflugers Arch 458:157-68. 2009
    ..Recent evidence suggests that WNK1, mitogen-activated protein kinases such as P38, ERK, and Src family protein tyrosine kinase are involved in mediating the effect of low K intake on apical K secretory channels...
  99. pmc Physiological significance of heme oxygenase in hypertension
    Jian Cao
    New York Medical College, Department of Pharmacology, Valhalla, NY 10595, United States
    Int J Biochem Cell Biol 41:1025-33. 2009
    ..The approaches detailed may prove to be seminal in the development of a new therapeutic strategy to treat hypertension...

Research Grants30

  1. Ether Lipids, Elcosanoids, and Lung Cell Pathophysiology
    CHRISTINA CARROLL LESLIE; Fiscal Year: 2013
    ..By using multidisciplinary approaches, we will determine the structural identity of lipid mediators, the molecular mechanisms involved in their production and how they function to regulate lung responses. ..
  2. CARDIOVASCULAR DYNAMICS AND THEIR CONTROL
    John E Hall; Fiscal Year: 2013
    ..End of Abstract) ..
  3. Signaling Processes Underlying Cardiovascular Function
    Jeffrey Robbins; Fiscal Year: 2013
    ..These projects are supported by 3 Cores: Core A: The Administrative Core;Core B: The Physiology Core and Core C: The Imaging-Cell Culture Core. (End of Abstract) ..
  4. Autocoids in Hypertension: Pathogenesis and End Organ Damage
    Oscar A Carretero; Fiscal Year: 2013
    ..Te PPG provides integration of our efforts, collaboration, sharing of ideas and expertise, thus accelerating acquisition of knowledge on the causes of hypertension and EOD. (End of Abstract) ..
  5. Expanding Excellence in Developmental Biology in Oklahoma
    Linda F Thompson; Fiscal Year: 2013
    ..abstract_text> ..