PHENOTYPIC MODULATION OF SMOOTH-MUSCLE CELLS DURING THE FORMATION OF NEOINTIMAL THICKENINGS IN THE RAT CAROTID-ARTERY AFTER BALLOON INJURY - AN ELECTRON-MICROSCOPIC AND STEREOLOGICAL STUDY

The formation of neointimal thickenings in the rat carotid artery afte r balloon injury was studied by a combination of electron-microscopic and stereological methods. All smooth muscle cells in the normal media had a contractile phenotype, the cytoplasm being dominated by myofila ments. Seven days after endothelial denudation, the smooth muscle cell s in the innermost part of the media had assumed a synthetic phenotype by loss of myofilaments and formation of a large endoplasmic reticulu m and Golgi complex. These cells moved through fine openings in the in ternal elastic lamina and gave rise to a growing neointima by prolifer ation and secretion of extracellular matrix components. Fourteen days after the operation, the neointima had almost reached its final size, and mitoses were no longer noted. Nevertheless, the cells maintained a synthetic phenotype with prominent secretory organelles, although myo filaments had started to become more abundant again. They were surroun ded by an extracellular matrix made up of collagen fibrils and coalesc ing patches of elastin. Thirty-five days after the operation, an endot helial cell layer had reformed and covered most of the luminal vessel surface. In parallel, the smooth muscle cells in the neointima had ret urned to a contractile phenotype with a cytoplasm dominated by myofila ments. These findings provide a morphological basis for further analys is of the cellular and molecular interactions involved in the formatio n of neointimal thickenings after endothelial injury, and for the sear ch for agents interfering with this process.