Inhibition of Neointimal Smooth Muscle Accumulation After Angioplasty by an Antibody to PDGF

TLDR

Restenosis after angioplasty is largely driven by neointimal smooth muscle accumulation, a process whose drivers are unclear but may involve platelet‑derived growth factor, a potent smooth muscle chemoattractant and mitogen present in platelets, endothelium, smooth muscle, and macrophages. In athymic nude rats, intimal lesion formation after balloon catheter deendothelialization was suppressed by a polyclonal antibody against PDGF. These results indicate that endogenous PDGF contributes to neointimal smooth muscle accumulation following balloon injury and may play a role in restenosis and atherogenesis.

Abstract

Approximately 30 to 40 percent of atherosclerotic coronary arteries treated by angioplasty or by bypass surgery occlude as a result of restenosis. This restenosis is due principally to the accumulation of neointimal smooth muscle cells, which is also a prominent feature of the advanced lesions of atherosclerosis. The factors responsible for the accumulation of intimal smooth muscle cells have not been identified. Platelet-derived growth factor (PDGF) is a potent smooth muscle chemoattractant and mitogen. It is present in platelets and can be formed by endothelium, smooth muscle, and monocyte-derived macrophages. The development of an intimal lesion in the carotid artery of athymic nude rats induced by intraarterial balloon catheter deendothelialization was inhibited by a polyclonal antibody to PDGF. These data demonstrate that endogenous PDGF is involved in the accumulation of neointimal smooth muscle cells associated with balloon injury and may be involved in restenosis after angioplasty, and perhaps in atherogenesis as well.