%0 Journal Article %1 Shiojima.2005 %A Shiojima, I. %A Sato, K. %A Izumiya, Y. %A Schiekofer, S. %A Ito, M. %A Liao, R. %A Colucci, W. S. %A Walsh, K. %D 2005 %J J.Clin.Invest %K & A Angiopoietin-2 Animals Capillaries Cardiomyopathies Cardiomyopathy Dilated Endothelial Expression Factor Failure Gene Growth Heart Human Humans Kinases Mice Myocardium Neovascularization Pathologic Protein-Serine-Threonine Proteins Proto-Oncogene Regulation Remodeling Research Transgenic Vascular Ventricular biosynthesis c-akt development enzymology genetics growth metabolism pathology protein %N 8 %P 2108-2118 %T Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure %U PM:16075055 %V 115 %X Although increased external load initially induces cardiac hypertrophy with preserved contractility, sustained overload eventually leads to heart failure through poorly understood mechanisms. Here we describe a conditional transgenic system in mice characterized by the sequential development of adaptive cardiac hypertrophy with preserved contractility in the acute phase and dilated cardiomyopathy in the chronic phase following the induction of an activated Akt1 gene in the heart. Coronary angiogenesis was enhanced during the acute phase of adaptive cardiac growth but reduced as hearts underwent pathological remodeling. Enhanced angiogenesis in the acute phase was associated with mammalian target of rapamycin-dependent induction of myocardial VEGF and angiopoietin-2 expression. Inhibition of angiogenesis by a decoy VEGF receptor in the acute phase led to decreased capillary density, contractile dysfunction, and impaired cardiac growth. Thus, both heart size and cardiac function are angi

@article{Shiojima.2005, abstract = {Although increased external load initially induces cardiac hypertrophy with preserved contractility, sustained overload eventually leads to heart failure through poorly understood mechanisms. Here we describe a conditional transgenic system in mice characterized by the sequential development of adaptive cardiac hypertrophy with preserved contractility in the acute phase and dilated cardiomyopathy in the chronic phase following the induction of an activated Akt1 gene in the heart. Coronary angiogenesis was enhanced during the acute phase of adaptive cardiac growth but reduced as hearts underwent pathological remodeling. Enhanced angiogenesis in the acute phase was associated with mammalian target of rapamycin-dependent induction of myocardial VEGF and angiopoietin-2 expression. Inhibition of angiogenesis by a decoy VEGF receptor in the acute phase led to decreased capillary density, contractile dysfunction, and impaired cardiac growth. Thus, both heart size and cardiac function are angi}, added-at = {2010-02-05T11:28:39.000+0100}, author = {Shiojima, I. and Sato, K. and Izumiya, Y. and Schiekofer, S. and Ito, M. and Liao, R. and Colucci, W. S. and Walsh, K.}, biburl = {https://www.bibsonomy.org/bibtex/278ebf10380bd78846174e6fb100f5608/kanefendt}, interhash = {56ce511607519a7fe4f8ebfe806b339c}, intrahash = {78ebf10380bd78846174e6fb100f5608}, journal = {J.Clin.Invest}, keywords = {& A Angiopoietin-2 Animals Capillaries Cardiomyopathies Cardiomyopathy Dilated Endothelial Expression Factor Failure Gene Growth Heart Human Humans Kinases Mice Myocardium Neovascularization Pathologic Protein-Serine-Threonine Proteins Proto-Oncogene Regulation Remodeling Research Transgenic Vascular Ventricular biosynthesis c-akt development enzymology genetics growth metabolism pathology protein}, number = 8, pages = {2108-2118}, timestamp = {2010-02-05T11:28:43.000+0100}, title = {Disruption of coordinated cardiac hypertrophy and angiogenesis contributes to the transition to heart failure}, url = {PM:16075055}, volume = 115, year = 2005 }