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

Abstract

The formation of neointimal thickenings in the rat carotid artery after 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 myofilaments. Seven days after endothelial denudation, the smooth muscle cells in the innermost part of the media had assumed a synthetic phenotype by loss of myofilaments and formation of a large endoplasmic reticulum and Golgi complex. These cells moved through fine openings in the internal elastic lamina and gave rise to a growing neointima by proliferation 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 myofilaments had started to become more abundant again. They were surrounded by an extracellular matrix made up of collagen fibrils and coalescing patches of elastin. Thirty-five days after the operation, an endothelial cell layer had reformed and covered most of the luminal vessel surface. In parallel, the smooth muscle cells in the neointima had returned to a contractile phenotype with a cytoplasm dominated by myofilaments. These findings provide a morphological basis for further analysis of the cellular and molecular interactions involved in the formation of neointimal thickenings after endothelial injury, and for the search for agents interfering with this process.

Contribution of the Helix-Loop-Helix Factor Id2 to Regulation of Vascular Smooth Muscle Cell Proliferation

“…1 proliferation is a key component of the response to vascular injury in atherosclerosis and restenosis in humans and following experimental angioplasty in animals (1)(2)(3). Several recent studies have focused interest on regulation of the cell cycle as a means of modulating this pathologic SMC growth (4 -6).…”

Novel Mechanisms of the Antiproliferative Effects of Amlodipine in Vascular Smooth Muscle Cells from Spontaneously Hypertensive Rats

“…We recently found that generation of Ang II in VSMC from SHR is associated with a change from the contractile to the synthetic phenotype, and that the change to the synthetic phenotype in SHR-derived VSMC also increases the expression of the growth factors of TGF-β1, PDGF A-chain, and bFGF through increased Ang II (33). VSMC proliferation and change to the synthetic phenotype contributes to the pathogenesis of atherosclerosis (34), neointimal formation after angioplasty (35) and hypertensive vascular diseases (36) in vivo.…”

The application of multiscale modelling to the process of development and prevention of stenosis in a stented coronary artery

“…Adult VSMCs are not terminally differentiated and may undergo major phenotypic changes in response to environmental stimuli (Fazekas et al 2007). Indeed, VSMCs may exhibit contractile or secretory phenotypes and have been observed to dedifferentiate following vascular injury (Campbell et al 1988;Thyberg et al 1995Thyberg et al , 1997. If one considers the contractile phenotype, the cells are spindle shaped and of the order of 80-200 mm long and 5 mm wide, whereas secretory VSMCs are smaller (approx.…”