RESTENOSIS - PATHOPHYSIOLOGY, TREATMENT A ND PREVENTION

Despite fifteen years of extensive research, we still do not know how to predict or prevent restenosis. Angioplasty induces lesions in the i ntima, media and sometimes adventitia, resulting in a cicatricial proc ess comprising proliferation and migration of smooth muscle cells towa rds the intima and secretion of extracellular matrix, leading to the f ormation of a neointima. Since angioplasty is associated with the simu ltaneous development of neointimal hyperplasia and restenosis, a cause and a effect relationship has therefore been proposed between neointi mal hyperplasia and restenosis. All the restenosis prevention strategi es based on inhibition of smooth muscle cell proliferation, which succ essfully limited restenosis in animal models have failed in man, due t o the hazardous extrapolations from experimental models which are very different from the atheromatous lesions observed in man, rather than to the use of animal models in general. It is reasonable to wonder whe ther we have not selected the wrong target: is smooth muscle cell prol iferation really responsible for restenosis ? Experimental results sup ported by histological and ultrasonographic data in man, show that the cicatricial process which induces restenosis consists of constrictive remodelling, which decreases the perimeter of the external elastic la mina and the lumen. The use of stents appears to be the primary strate gy designed to limit restenosis and prevent constrictive remodelling i n man, even if it stimulates neointimal hyperplasia. Progress in the u nderstanding of the mechanisms of postangioplasty remodelling open new perspectives in the prevention of restenosis.