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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2009;29:1060.)
© 2009 American Heart Association, Inc.

Integrative Physiology/Experimental Medicine

Insulin Increases Reendothelialization and Inhibits Cell Migration and Neointimal Growth After Arterial Injury

Danna M. Breen; Kalam K. Chan; Jiwanjeet K. Dhaliwall; Michael R. Ward; Nael Al Koudsi; Loretta Lam; Melissa De Souza; Husam Ghanim; Paresh Dandona; Duncan J. Stewart; Michelle P. Bendeck; Adria Giacca

From the Departments of Physiology (D.M.B., K.K.C., 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., D.J.S., A.G.), University of Toronto, St. Michael’s Hospital (M.R.W., D.J.S.), Toronto, Canada; and the Division of Endocrinology, Diabetes, and Metabolism (H.G., P.D.), State University of New York at Buffalo, Kaleida Health, Buffalo, NY.

Correspondence to Dr Adria Giacca, University of Toronto, Department of Physiology, Medical Sciences Building, Toronto, Ontario, Canada M5S 1A8. 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 or 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.

Insulin has both growth-promoting and vasculoprotective effects in vitro, however the predominant effect in vivo is unclear. After arterial injury in rats insulin decreased neointimal growth and cell migration, and increased SMC differentiation markers, reendothelialization, and the number of circulating progenitor cells. Thus, insulin has a predominant vasculoprotective effect in vivo.

Key Words: insulin • vascular smooth muscle cell • migration • neointima • angioplasty • reendothelialization