Insulin resistance increases PAI-1 in the heart.
To determine whether insulin resistance increases expression of plasminogen activator inhibitor type-1 (PAI-1) in the heart, studies were performed in 22 mice with and 38 without myocardial infarction. Insulin resistance in transgenic animals genetically rendered insulin resistant was confirmed with the use of intraperitoneal glucose tolerance tests. Myocardial infarction was induced by coronary ligation, verified echocardiographically, and quantified by assay of depletion of creatine kinase (CK) from the left ventricle 2 weeks later. PAI-1 increased markedly in zones of infarction to 10.4+/-2.1 (SF) and significantly more to 27.3+/-3.6 in normal and insulin resistant mice compared with 0.45+/-0.04 and 0.50+/-0.03 in normal myocardium. Thus, insulin resistance induced accumulation of PAI-1 in the heart, particularly in zones of infarction. Such increases may contribute to fibrosis and diastolic dysfunction typical late after infarction in patients with insulin resistance.
Sobel
Burton E
BE
University of Vermont, Cardiovascular Research Institute Burlington, VT, USA. burt.sobel@vtmednet.org
Schneider
David J
DJ
Lee
Yong-Ho
YH
Pratley
Richard E
RE
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D004452:Echocardiography; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism*
D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1