STAT3-mediated activation of myocardial capillary growth.
Proper perfusion and vessel integrity are key requisites for myocardial homeostasis. In this regard, myocardial angiogenesis occurs in physiologic and pathologic conditions. Failure in this process and the resulting deficient oxygen supply induce loss and degeneration of cardiomyocytes, atrophy, and interstitial fibrosis and are viewed as a primary cause of myocardial dysfunction and heart failure. In this review, signal transducer and activator of transcription 3 (STAT3) is highlighted as a regulator of proangiogenic circuits promoting vessel formation in the adult heart under physiologic and pathophysiologic conditions. Specifically, STAT3 regulates proangiogenic vascular endothelial growth factor (VEGF) expression and activity in the postnatal heart and suppresses an antiangiogenic and profibrotic gene program by controlling autocrine and paracrine circuits. In addition, signaling through STAT3 represents a necessary survival pathway for cardiomyocytes and endothelial cells and seems to promote cytokine-mediated cardiac angiogenesis. In contrast, STAT3 seems not to be required for differentiation processes of embryonic or adult endothelial progenitor cells. In summary, the properly timed expression and activation of STAT3 play a critical role on cardiac angiogenesis and involve the subtle control of paracrine and autocrine mechanisms regulating angiogenic circuits and survival pathways of cardiomyocytes and endothelial cells.
Hilfiker-Kleiner
Denise
D
Department of Cardiology and Angiology, Medical School Hannover, Carl-Neuberg Strasse 1, 30625 Hannover, Germany. hilfiker.denise@mh-hannover.de
Limbourg
Anne
A
Drexler
Helmut
H
D000818:Animals; D002196:Capillaries; D002303:Cardiac Output, Low / Q000188:drug therapy; D003331:Coronary Vessels / Q000196:embryology* / Q000254:growth & development*; D016207:Cytokines / Q000378:metabolism; D047108:Embryonic Development; D006321:Heart / Q000503:physiopathology; D006801:Humans; D008833:Microcirculation; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic / Q000235:genetics / Q000502:physiology; D050796:STAT3 Transcription Factor / Q000378:metabolism / Q000502:physiology*; D013312:Stress, Physiological / Q000503:physiopathology
D016207:Cytokines; D050796:STAT3 Transcription Factor