Genomes and Genes
Experts and Doctors on cardiac myocytes in Cincinnati, Ohio, United States
Locale: Cincinnati, Ohio, United States
Topic: cardiac myocytes
- Diwan A, Krenz M, Syed F, Wansapura J, Ren X, Koesters A, et al. Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest. 2007;117:2825-33 pubmed..These studies identify postischemic apoptosis by myocardial Bnip3 as a major determinant of ventricular remodeling in the infarcted heart, suggesting that Bnip3 may be an attractive therapeutic target. ..
- Melendez J, Turner C, Avraham H, Steinberg S, Schaefer E, Sussman M. Cardiomyocyte apoptosis triggered by RAFTK/pyk2 via Src kinase is antagonized by paxillin. J Biol Chem. 2004;279:53516-23 pubmed
- Bushdid P, Osinska H, Waclaw R, Molkentin J, Yutzey K. NFATc3 and NFATc4 are required for cardiac development and mitochondrial function. Circ Res. 2003;92:1305-13 pubmed..Together, these data support the hypothesis that loss of NFAT activity in the heart results in a deficiency in mitochondrial energy metabolism required for cardiac morphogenesis and function. ..
- Yuan Q, Fan G, Dong M, Altschafl B, Diwan A, Ren X, et al. Sarcoplasmic reticulum calcium overloading in junctin deficiency enhances cardiac contractility but increases ventricular automaticity. Circulation. 2007;115:300-9 pubmed..Thus, normal intracellular Ca cycling relies on maintenance of junctin levels and an intricate balance among the components in the sarcoplasmic reticulum quaternary Ca-signaling complex. ..
- Diwan A, Wansapura J, Syed F, Matkovich S, Lorenz J, Dorn G. Nix-mediated apoptosis links myocardial fibrosis, cardiac remodeling, and hypertrophy decompensation. Circulation. 2008;117:396-404 pubmed publisher..35%; P=0.032). Nix-induced cardiomyocyte apoptosis is a major determinant of adverse remodeling in pathological hypertrophies, a finding that suggests therapeutic value for apoptosis inhibition to prevent cardiomyopathic decompensation. ..
- Sanbe A, James J, Tuzcu V, Nas S, Martin L, Gulick J, et al. Transgenic rabbit model for human troponin I-based hypertrophic cardiomyopathy. Circulation. 2005;111:2330-8 pubmed
- Baines C, Kaiser R, Purcell N, Blair N, Osinska H, Hambleton M, et al. Loss of cyclophilin D reveals a critical role for mitochondrial permeability transition in cell death. Nature. 2005;434:658-62 pubmed..Thus, cyclophilin D and the mitochondrial permeability transition are required for mediating Ca2+- and oxidative damage-induced cell death, but not Bcl-2 family member-regulated death. ..
- Chu G, Egnaczyk G, Zhao W, Jo S, Fan G, Maggio J, et al. Phosphoproteome analysis of cardiomyocytes subjected to beta-adrenergic stimulation: identification and characterization of a cardiac heat shock protein p20. Circ Res. 2004;94:184-93 pubmed..These findings suggest that cardiomyocytes undergo significant posttranslational modification via phosphorylation in a multitude of proteins to dynamically fine-tune cardiac responses to beta-adrenergic signaling. ..
- Sanbe A, Osinska H, Villa C, Gulick J, Klevitsky R, Glabe C, et al. Reversal of amyloid-induced heart disease in desmin-related cardiomyopathy. Proc Natl Acad Sci U S A. 2005;102:13592-7 pubmed..Blocking cardiac amyloid oligomer formation, even after cardiac dysfunction presents, may be a therapeutic strategy in DRM as well as in other types of cardiac disease in which significant amyloid accumulation occurs. ..
- Dai Y, Xu J, Molkentin J. The DnaJ-related factor Mrj interacts with nuclear factor of activated T cells c3 and mediates transcriptional repression through class II histone deacetylase recruitment. Mol Cell Biol. 2005;25:9936-48 pubmed..Collectively, our results define a novel response pathway whereby NFATc3 is negatively regulated by class II histone deacetylases through the DnaJ (heat shock protein-40) superfamily member Mrj. ..
- Heineke J, Auger Messier M, Xu J, Sargent M, York A, Welle S, et al. Genetic deletion of myostatin from the heart prevents skeletal muscle atrophy in heart failure. Circulation. 2010;121:419-25 pubmed publisher..Myostatin released from cardiomyocytes induces skeletal muscle wasting in heart failure. Targeted inhibition of myostatin in cardiac cachexia might be a therapeutic option in the future. ..
- Fan G, Yuan Q, Zhao W, Chu G, Kranias E. Junctin is a prominent regulator of contractility in cardiomyocytes. Biochem Biophys Res Commun. 2007;352:617-22 pubmed..Importantly, there were no alterations in other Ca-cycling protein levels when junctin levels were either decreased or increased. These findings suggest that junctin plays a prominent role in cardiomyocyte Ca-cycling and contractility. ..
- Braz J, Bueno O, Liang Q, Wilkins B, Dai Y, Parsons S, et al. Targeted inhibition of p38 MAPK promotes hypertrophic cardiomyopathy through upregulation of calcineurin-NFAT signaling. J Clin Invest. 2003;111:1475-86 pubmed..Collectively, these observations indicate that reduced p38 signaling in the heart promotes myocyte growth through a mechanism involving enhanced calcineurin-NFAT signaling. ..
- Dai Y, Xu M, Wang Y, Pasha Z, Li T, Ashraf M. HIF-1alpha induced-VEGF overexpression in bone marrow stem cells protects cardiomyocytes against ischemia. J Mol Cell Cardiol. 2007;42:1036-44 pubmed..Bone marrow stem cells protect cardiomyocytes by up-regulation of VEGF via activating HIF-1alpha. ..
- Melendez J, Welch S, Schaefer E, Moravec C, Avraham S, Avraham H, et al. Activation of pyk2/related focal adhesion tyrosine kinase and focal adhesion kinase in cardiac remodeling. J Biol Chem. 2002;277:45203-10 pubmed..Collectively, these results delineate a cardiomyocyte signaling pathway associated with dilation that has potential relevance for cardiac remodeling, focal adhesion reorganization, and loss of contractility. ..
- Nakamura T, Colbert M, Krenz M, Molkentin J, Hahn H, Dorn G, et al. Mediating ERK 1/2 signaling rescues congenital heart defects in a mouse model of Noonan syndrome. J Clin Invest. 2007;117:2123-32 pubmed
- Maillet M, Purcell N, Sargent M, York A, Bueno O, Molkentin J. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 2008;283:31246-55 pubmed publisher..These results demonstrate that ERK1/2 signaling is physiologically restrained by DUSP6 in coordinating cellular development and survival characteristics, directly impacting disease-responsiveness in adulthood. ..
- Goodman M, Koch S, Fuller Bicer G, Butler K. Regulating RISK: a role for JAK-STAT signaling in postconditioning?. Am J Physiol Heart Circ Physiol. 2008;295:H1649-56 pubmed publisher..POC induces myocardial functional protection by activating the RISK pathway. JAK-STAT signaling, however, is insufficient for effective POC without PI3K-Akt activation. ..
- Chen G, Zhou X, Nicolaou P, Rodriguez P, Song G, Mitton B, et al. A human polymorphism of protein phosphatase-1 inhibitor-1 is associated with attenuated contractile response of cardiomyocytes to beta-adrenergic stimulation. FASEB J. 2008;22:1790-6 pubmed publisher..These findings suggest that the human G147D PPI-1 can attenuate responses of cardiomyocytes to beta-adrenergic agonists by decreasing PLN phosphorylation and therefore may contribute to deteriorated function in heart failure. ..
- Bueno O, Lips D, Kaiser R, Wilkins B, Dai Y, Glascock B, et al. Calcineurin Abeta gene targeting predisposes the myocardium to acute ischemia-induced apoptosis and dysfunction. Circ Res. 2004;94:91-9 pubmed..These results represent the first genetic loss-of-function data showing a prosurvival role for calcineurin-NFAT signaling in the heart. ..
- Hahn H, Marreez Y, Odley A, Sterbling A, Yussman M, Hilty K, et al. Protein kinase Calpha negatively regulates systolic and diastolic function in pathological hypertrophy. Circ Res. 2003;93:1111-9 pubmed..These results define pathological roles for PKCalpha as a negative regulator of ventricular systolic and diastolic function. ..
- Fan G, Gregory K, Zhao W, Park W, Kranias E. Regulation of myocardial function by histidine-rich, calcium-binding protein. Am J Physiol Heart Circ Physiol. 2004;287:H1705-11 pubmed..Collectively, these data indicate that alterations in expression levels of HRC are associated with impaired cardiac SR Ca homeostasis and contractile function. ..
- Sengupta A, Molkentin J, Yutzey K. FoxO transcription factors promote autophagy in cardiomyocytes. J Biol Chem. 2009;284:28319-31 pubmed publisher..Together these results provide evidence for an important role for FoxO1 and FoxO3 in regulating autophagy and cell size in cardiomyocytes. ..
- Maloyan A, Gulick J, Glabe C, Kayed R, Robbins J. Exercise reverses preamyloid oligomer and prolongs survival in alphaB-crystallin-based desmin-related cardiomyopathy. Proc Natl Acad Sci U S A. 2007;104:5995-6000 pubmed..The data demonstrate that voluntary exercise slows the progression to HF in the CryAB(R120G) DRM model and that PAO accumulation is mediated, at least in part, by decreased neprilysin activity. ..
- Xu J, Gong N, Bodi I, Aronow B, Backx P, Molkentin J. Myocyte enhancer factors 2A and 2C induce dilated cardiomyopathy in transgenic mice. J Biol Chem. 2006;281:9152-62 pubmed
- Wang X, Zhao T, Huang W, Wang T, Qian J, Xu M, et al. Hsp20-engineered mesenchymal stem cells are resistant to oxidative stress via enhanced activation of Akt and increased secretion of growth factors. Stem Cells. 2009;27:3021-31 pubmed publisher..Taken together, these data support the premise that genetic modification of MSCs before transplantation could be salutary for treating myocardial infarction. ..
- Fan G, Chu G, Mitton B, Song Q, Yuan Q, Kranias E. Small heat-shock protein Hsp20 phosphorylation inhibits beta-agonist-induced cardiac apoptosis. Circ Res. 2004;94:1474-82 pubmed..These findings suggest that Hsp20 and its phosphorylation at Ser16 may provide cardioprotection against beta-agonist-induced apoptosis. Thus, Hsp20 may represent a novel therapeutic target in the treatment of heart failure. ..
- Wu X, Chang B, Blair N, Sargent M, York A, Robbins J, et al. Plasma membrane Ca2+-ATPase isoform 4 antagonizes cardiac hypertrophy in association with calcineurin inhibition in rodents. J Clin Invest. 2009;119:976-85 pubmed publisher..Thus, Pmca4b likely reduces the local Ca2+ signals involved in reactive cardiomyocyte hypertrophy via calcineurin regulation. ..
- Braz J, Gregory K, Pathak A, Zhao W, Sahin B, Klevitsky R, et al. PKC-alpha regulates cardiac contractility and propensity toward heart failure. Nat Med. 2004;10:248-54 pubmed..Thus, PKC-alpha functions as a nodal integrator of cardiac contractility by sensing intracellular Ca(2+) and signal transduction events, which can profoundly affect propensity toward heart failure. ..
- Maloyan A, Sanbe A, Osinska H, Westfall M, Robinson D, Imahashi K, et al. Mitochondrial dysfunction and apoptosis underlie the pathogenic process in alpha-B-crystallin desmin-related cardiomyopathy. Circulation. 2005;112:3451-61 pubmed
- Waggoner J, Ginsburg K, Mitton B, Haghighi K, Robbins J, Bers D, et al. Phospholamban overexpression in rabbit ventricular myocytes does not alter sarcoplasmic reticulum Ca transport. Am J Physiol Heart Circ Physiol. 2009;296:H698-703 pubmed publisher..In larger mammals, a higher fraction of SERCA2a pumps are regulated by phospholamban, and this may influence therapeutic strategies to enhance cardiac contractility and functional cardiac reserve. ..
- Fuller Bicer G, Varadi G, Koch S, Ishii M, Bodi I, Kadeer N, et al. Targeted disruption of the voltage-dependent calcium channel alpha2/delta-1-subunit. Am J Physiol Heart Circ Physiol. 2009;297:H117-24 pubmed publisher..This is a novel model for studying the function of the alpha(2)/delta-1-subunit and will be of importance in the development of new pharmacological therapies. ..
- Purevjav E, Varela J, Morgado M, Kearney D, Li H, Taylor M, et al. Nebulette mutations are associated with dilated cardiomyopathy and endocardial fibroelastosis. J Am Coll Cardiol. 2010;56:1493-502 pubmed publisher..Nebulette is a new susceptibility gene for endocardial fibroelastosis and DCM. Different mutations in nebulette trigger specific mechanisms, converging to a common pathological cascade leading to endocardial fibroelastosis and DCM. ..
- Fan G, Zhou X, Wang X, Song G, Qian J, Nicolaou P, et al. Heat shock protein 20 interacting with phosphorylated Akt reduces doxorubicin-triggered oxidative stress and cardiotoxicity. Circ Res. 2008;103:1270-9 pubmed publisher..Thus, Hsp20 may constitute a new therapeutic target in ameliorating the cardiotoxic effects of DOX treatment in cancer patients. ..
- Purcell N, Darwis D, Bueno O, Müller J, Schüle R, Molkentin J. Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes. Mol Cell Biol. 2004;24:1081-95 pubmed..Collectively, these results suggest that FHL2 serves a repressor function in cardiomyocytes through its ability to inhibit ERK1/2 transcriptional coupling. ..
- Heineke J, Auger Messier M, Xu J, Oka T, Sargent M, York A, et al. Cardiomyocyte GATA4 functions as a stress-responsive regulator of angiogenesis in the murine heart. J Clin Invest. 2007;117:3198-210 pubmed..To our knowledge, these results demonstrate [corrected] a previously unrecognized function for GATA4 as a regulator of cardiac angiogenesis through a nonhypoxic, load, and/or disease-responsive mechanism. ..
- Molkentin J. A friend within the heart: natriuretic peptide receptor signaling. J Clin Invest. 2003;111:1275-7 pubmed
- Oka T, Xu J, Kaiser R, Melendez J, Hambleton M, Sargent M, et al. Genetic manipulation of periostin expression reveals a role in cardiac hypertrophy and ventricular remodeling. Circ Res. 2007;101:313-21 pubmed..These are the first genetic data detailing the function of Pn in the adult heart as a regulator of cardiac remodeling and hypertrophy. ..
- Sanna B, Bueno O, Dai Y, Wilkins B, Molkentin J. Direct and indirect interactions between calcineurin-NFAT and MEK1-extracellular signal-regulated kinase 1/2 signaling pathways regulate cardiac gene expression and cellular growth. Mol Cell Biol. 2005;25:865-78 pubmed..Collectively, these results indicate that calcineurin-NFAT and MEK1-ERK1/2 pathways constitute a codependent signaling module in cardiomyocytes that coordinately regulates the growth response through two distinct mechanisms. ..
- Wu X, Eder P, Chang B, Molkentin J. TRPC channels are necessary mediators of pathologic cardiac hypertrophy. Proc Natl Acad Sci U S A. 2010;107:7000-5 pubmed publisher..Thus, TRPC channels are necessary mediators of pathologic cardiac hypertrophy, in part through a calcineurin-NFAT signaling pathway. ..
- Nakayama H, Bodi I, Maillet M, DeSantiago J, Domeier T, Mikoshiba K, et al. The IP3 receptor regulates cardiac hypertrophy in response to select stimuli. Circ Res. 2010;107:659-66 pubmed publisher..These results indicate that IP(3)-mediated Ca(2+) release plays a central role in regulating cardiac hypertrophy downstream of GPCR signaling, in part, through a calcineurin-dependent mechanism. ..
- Nakayama H, Chen X, Baines C, Klevitsky R, Zhang X, Zhang H, et al. Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure. J Clin Invest. 2007;117:2431-44 pubmed