Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro.
Hypertrophy is a fundamental adaptive process employed by postmitotic cardiac and skeletal muscle in response to mechanical load. How muscle cells convert mechanical stimuli into growth signals has been a long-standing question. Using an in vitro model of load (stretch)-induced cardiac hypertrophy, we demonstrate that mechanical stretch causes release of angiotensin II (Ang II) from cardiac myocytes and that Ang II acts as an initial mediator of the stretch-induced hypertrophic response. The results not only provide direct evidence for the autocrine mechanism in load-induced growth of cardiac muscle cells, but also define the pathophysiological role of the local (cardiac) renin-angiotensin system.
Sadoshima
J
J
Molecular Medicine Division, Beth Israel Hospital, Boston, Massachusetts.
Xu
Y
Y
Slayter
H S
HS
Izumo
S
S
D000199:Actins / Q000235:genetics; D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000502:physiology*; D000808:Angiotensinogen / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D009320:Atrial Natriuretic Factor / Q000235:genetics; D006332:Cardiomegaly / Q000473:pathology*; D002478:Cells, Cultured; D003594:Cytoplasmic Granules / Q000378:metabolism; D016232:Endothelins / Q000378:metabolism; D005786:Gene Expression Regulation; D016762:Genes, fos; D006984:Hypertrophy; D066298:In Vitro Techniques; D008465:Mechanoreceptors / Q000502:physiology; D009206:Myocardium / Q000166:cytology* / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D012083:Renin / Q000378:metabolism; D013314:Stress, Mechanical
D000199:Actins; D016232:Endothelins; D012333:RNA, Messenger; D000808:Angiotensinogen; D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; D012083:Renin