Plasminogen activator inhibitor type-1 -- a potential link between heart failure and diabetes

Feb 24, 2009

Researchers at the University of Vermont Cardiovascular Research Institute, Colchester, Vermont have found that increased expression in the heart of plasminogen activator inhibitor type-1 (PAI-1) is profibrotic. The results, which appear in the March 2009 issue of Experimental Biology and Medicine, implicate PAI-1 overexpression, known to accompany insulin resistance and type 2 diabetes, as a factor contributing to the high incidence of heart failure after myocardial infarction in people with diabetes.

The research team, Dr. A.K.M. Tarikuz Zaman, a research associate, Mr. Christopher J. French, medical and graduate student, Dr. David J. Schneider, Professor of Medicine and Director of the Cardiology and Vascular Biology Units, and Dr. Burton E. Sobel, Professor of Medicine and Director of the Cardiovascular Research Institute, performed studies in 10 week old mice subjected to coronary occlusion.

Controls and PAI-1 overexpressing mice congenic on a C57BL6 background had comparable PAI-1 content in left ventricular myocardium despite a marked elevation of PAI-1 in plasma in the latter. 6 weeks after coronary occlusion the PAI-1 overexpressing mice exhibited a 2-fold increase in left ventricular (LV) PAI-1 content. Histochemical analysis demonstrated 33% more LV fibrosis as well. The increased fibrosis associated with increased PAI-1 was accompanied by functional derangements including diminished LV wall thickness in both diastole and systole, increased end systolic LV dimensions, depressed fractional shortening, a greater impairment of LV segmental function, and greater transmitral E-wave amplitude.

In summary, overexpression of PAI-1 in the heart altered the response of the left ventricle to myocardial infarction. It led to increased expression of PAI-1 late after coronary occlusion accompanied by increased fibrosis and functional derangements indicative of both systolic and diastolic dysfunction. Dr. Sobel said that "in concert with our previously reported findings demonstrating increased expression of PAI-1 in the heart in transgenic mice rendered insulin resistant, these results suggest that the markedly increased incidence and severity of heart failure following myocardial infarction in patients with insulin resistance and type 2 diabetes may reflect in part adverse consequences of increased PAI-1 expression in the heart predisposing to fibrosis and impairment performance of the left ventricle."

Dr. Steven R. Goodman, Editor-in-Chief of Experimental Biology and Medicine said "these elegant studies by Dr. Sobel and colleagues provide substantial insight into the mechanisms by which type 2 diabetes, with the resulting increase in PAI-1 in the heart, can lead to increased incidence and severity of heart failure following myocardial infarction. This is a major step forward in our understanding of the linkage between diabetes and cardiovascular disease".

Source: Society for Experimental Biology and Medicine

Explore further: Newly discovered hormone mimics the effects of exercise

add to favorites email to friend print save as pdf

Related Stories

Driverless shuttle will be on the move in UK

Feb 22, 2015

(Phys.org) —"Autonomous public transport" is on the minds of planners who envision self-driving vehicles that would cross over short distances, suited for airport transport, industrial sites, theme parks ...

Korean tech start-ups offer life beyond Samsung

Feb 23, 2015

As an engineering major at Seoul's Yonsei University, Yoon Ja-Young was perfectly poised to follow the secure, lucrative and socially prized career path long-favoured by South Korea's elite graduates.

Recommended for you

Newly discovered hormone mimics the effects of exercise

19 hours ago

Scientists at the USC Leonard Davis School of Gerontology have discovered a new hormone that fights the weight gain caused by a high-fat Western diet and normalizes the metabolism - effects commonly associated ...

User comments : 0

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.