Reduced intimal thickening following alpha v beta 3 blockade is associatedwith smooth muscle cell apoptosis

The adhesion integrin alpha v beta 3 is expressed by both activated endothe lial cells (ECs) and smooth muscle cells (SMCs). Peptide and antibody antag onists of alpha v beta 3 have been shown to block angiogenesis by initiatin g unscheduled programmed cell death of proliferating ECs. The present study was designed to determine if antagonism of alpha v beta 3 immediately foll owing balloon injury might similarly lead to programmed cell death among ac tivated SMCs, and thereby inhibit intimal thickening. LM609, a monoclonal a ntibody antagonist of alpha v beta 3, was administered locally and/or syste mically immediately after balloon angioplasty in a rabbit model of vascular injury. Immunohistochemical studies documented that LM609, even when admin istered systemically, localized to sites of vascular injury. LM609 administ ered immediately following balloon injury of the external iliac artery mark edly reduced intimal thickening at 2 and 4 wk post-injury. Apoptosis was ab undant where balloon injury resulted in expression of alpha v beta 3. At bo th 2 and 4 wk, reendothelialization at the site of balloon injury was not r etarded in LM609-treated rabbits versus controls. Thus, blockade of alpha v beta 3 inhibits intimal thickening when administered immediately following balloon injury. This favorable impact on neointimal thickening is associat ed with apoptosis of activated SMCs expressing alpha v beta 3. These findin gs may explain the reduction in restenosis observed clinically following be ta 3 integrin blockade.