Abstract:
:The transcription factor signal transducer and activator of transcription 3 (STAT3) participates in a wide variety of physiological processes and directs seemingly contradictory responses such as proliferation and apoptosis. To elucidate its role in the heart, we generated mice harboring a cardiomyocyte-restricted knockout of STAT3 using Cre/loxP-mediated recombination. STAT3-deficient mice developed reduced myocardial capillary density and increased interstitial fibrosis within the first 4 postnatal months, followed by dilated cardiomyopathy with impaired cardiac function and premature death. Conditioned medium from STAT3-deficient cardiomyocytes inhibited endothelial cell proliferation and increased fibroblast proliferation, suggesting the presence of paracrine factors attenuating angiogenesis and promoting fibrosis in vitro. STAT3-deficient mice showed enhanced susceptibility to myocardial ischemia/reperfusion injury and infarction with increased cardiac apoptosis, increased infarct sizes, and reduced cardiac function and survival. Our study establishes a novel role for STAT3 in controlling paracrine circuits in the heart essential for postnatal capillary vasculature maintenance, interstitial matrix deposition balance, and protection from ischemic injury and heart failure.
journal_name
Circ Resjournal_title
Circulation researchauthors
Hilfiker-Kleiner D,Hilfiker A,Fuchs M,Kaminski K,Schaefer A,Schieffer B,Hillmer A,Schmiedl A,Ding Z,Podewski E,Podewski E,Poli V,Schneider MD,Schulz R,Park JK,Wollert KC,Drexler Hdoi
10.1161/01.RES.0000134921.50377.61subject
Has Abstractpub_date
2004-07-23 00:00:00pages
187-95issue
2eissn
0009-7330issn
1524-4571pii
01.RES.0000134921.50377.61journal_volume
95pub_type
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