Proliferation of smooth muscle cells after vascular injury is inhibited by an antibody against basic fibroblast growth factor.

TLDR

Smooth muscle cell proliferation drives vascular lesion formation, yet direct evidence linking growth factors to arterial injury remains lacking, as balloon catheter injury in rats induces medial cell death followed by proliferation and intimal lesion development. The study tests whether injury‑released mitogens, particularly basic fibroblast growth factor (bFGF), stimulate smooth muscle cell proliferation. They identified bFGF immunocytochemically in rat carotid smooth muscle and endothelial cells and used a neutralizing antibody to block its activity. Neutralizing bFGF reduced smooth muscle cell proliferation by about 80% after balloon injury, but the intimal lesion size was unchanged, confirming bFGF as the key mitogen driving post‑injury smooth muscle growth and suggesting why endarterectomy and angioplasty often fail.

Abstract

Proliferation of smooth muscle cells (SMCs) represents an important event in vascular lesion formation. Despite the common belief that growth factors contribute to the development of the atherosclerotic plaque, until now there has been no direct evidence for a role of mitogens in the development of arterial lesions. Balloon catheter injury of the rat carotid artery is accompanied by death of medial SMCs and is typically followed by proliferation of SMCs with subsequent formation of an intimal lesion. Our hypothesis is that injury causes mitogens to be released from dead cells, which then stimulate cell proliferation. One such mitogen that may be important in this process is basic fibroblast growth factor (bFGF), which can be detected immunocytochemically in SMCs and endothelial cells of adult rat carotid arteries. Systemic injection of a neutralizing antibody against bFGF prior to balloon catheterization significantly decreased the induced SMC proliferation by approximately 80%. The intimal lesion that developed within 8 days after injury, however, was not significantly reduced. The results of this study support the concept that endogenous bFGF is the major mitogen controlling the growth of vascular smooth muscle cells following injury. These data may have implications for the observed failure of endarterectomy and angioplasty procedures.