on April 9, 2009
Published online before print April 9, 2009, doi: 10.1161/ATVBAHA.109.185447
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Submitted on August 4, 2004
Accepted on March 30, 2009
Insulin Increases Reendothelialization and Inhibits Cell Migration and Neointimal Growth After Arterial Injury
Kalam K. Chan ;
From the Departments of Physiology (K.K.C., D.M.B., J.K.D., N.A.K., L.L., M.D.S., A.G.), Medicine (M.P.B., A.G.), Laboratory Medicine and Pathobiology (M.P.B.), Institute of Medical Sciences (M.R.W.), University of Toronto, St. Michael';s Hospital (M.R.W., D.S.), Toronto, Canada; and the Division of Endocrinology, Diabetes, and Metabolism (H.G., P.D.P.), State University of New York at Buffalo, Kaleida Health.
* To whom correspondence should be addressed. E-mail: adria.giacca{at}utoronto.ca.
Objective—Insulin has both growth-promoting and protective vascular effects in vitro, however the predominant effect in vivo is unclear. We investigated the effects of insulin in vivo on neointimal growth after arterial injury.
Methods and Results—Rats were given subcutaneous control (C) or insulin implants (3U/d;I) 3 days before arterial (carotid and aortic) balloon catheter injury. Normoglycemia was maintained by oral glucose and, after surgery, by intraperitoneal glucose infusion (saline in C). Insulin decreased intimal area (P<0.01) but did not change intimal cell proliferation or apoptosis. However, insulin inhibited cell migration into the intima (P<0.01) and increased expression of smooth muscle cell (SMC) differentiation markers (P<0.05). Insulin also increased reendothelialization (P<0.01) and the number of circulating progenitor cells (P<0.05).
Conclusions—These results are the first demonstration that insulin has a protective effect on both SMC and endothelium in vivo, resulting in inhibition of neointimal growth after vessel injury.
Key words: insulin • vascular smooth muscle cell • migration • neointima • angioplasty • reendothelialization