Intimal injury in vivo activates vascular smooth muscle cell migration and explant outgrowth in vitro.

Abstract

In vivo induced endothelial injury results in an intimal thickening, mainly caused by stimulation of smooth muscle cells (SMC), which migrate into, and proliferate in, the denuded intima. We evaluated the manifestation and persistence of this stimulus in several in vitro explant and growth assays using aortic explants from either balloon catheter-injured rats or from sham-operated controls. SMC outgrowth from control explants started 48 hours after explantation, became half-maximal after 96 hours, with 74% of the explants showing outgrowth. Explants from balloon-injured aortas showed SMC outgrowth within 24 hours, became half-maximal after 48 hours, with 92% of the explants showing outgrowth. An interval of 4 to 7 days between balloon injury and sacrifice was optimal for obtaining accelerated outgrowth, while a 1-day interval showed a weak stimulation and a 21-day interval had no such effect. The in vivo stimulated cells grew more rapidly, resulting in a greater colony size per explant, and they became temporarily serum-independent. Increased growth rate persisted up to the second subculture but returned to normal in subsequent passages. 2 Altered endothelial integrity is thought to expose the underlying SMC to stimuli that induce migration of the SMC through the internal elastic lamina to the intima, where they proliferate.34 Approximately 3 to 4 days after experimental injury, 56 activated or modulated SMC 7 ' 8 appear at the luminal surface and form an intimal thickening that displays many features of an atherosclerotic plaque.Cell culture techniques are now widely used to study the growth kinetics and morphology of SMC. 24 Differences in SMC outgrowth after mechanical injury of the rabbit aorta have also been reported briefly. 25 We have extended this work in the studies reported here by quantifying SMC migration and proliferation in explant cultures and subcultivations after balloon injury of the rat aorta. These studies show that SMC migration and proliferation in vitro are accelerated and enhanced in response to the in vivo injury. Furthermore, the in vivo stimulus renders the SMC temporarily serum-independent.

Growth Factors Stimulate Neointimal Cells In Vitro and Increase the Thickness of the Neointima Formed at the Neck of Porcine Aneurysms Treated by Embolization

“…3 Neointimal cells recovered from vascular injury models have been reported as cells that proliferate faster and secrete more extracellular matrix proteins than medial vascular smooth muscle cells, characteristics that persist for many passages in vitro. 45,46 Aneurysmal neointimal cells manifested no significant increase in DNA synthesis or cell proliferation compared with carotid smooth muscle cells and presented decreased basal collagen synthesis in the present study. Reports have suggested that neointimal cells recovered after balloon injury have a blunted response to GFs compared with normal vascular smooth muscle cells.…”

Histopathologic Evaluation of Arterial Wall Response to 5 Neurovascular Mechanical Thrombectomy Devices in a Swine Model

“…27 These results are substantiated by those of other studies that have shown that smooth muscle cells are normally quiescent with respect to proliferation but that deep injuries result in the expression of a phenotype of vascular smooth-muscle cells that exhibits a high proliferative response to other mitogens. 28 Given these results, the aspiration device resulted in a less traumatic acute injury in the vascular wall. However, this study did not analyze the vascular recanalization rate; therefore, deducing that the aspiration device would have better functional results is not appropriate.…”

Fabric organization of the subendothelium of the human brain artery by polarized-light microscopy.

“…Smooth muscle cells are dynamic in their organization as illustrated by their infiltration and proliferation in the subendothelium with atherosclerosis, aging, or wall injury. 16 - 17 When grown in culture, smooth muscle cells orient themselves in small colonies or fasciculi of parallel cells, with random overall orientations of these colonies. However, as they proliferate in the subendothelial layer, their orientation is far from random and may be influenced by pulsating circumferential strain, with evidence for this proposal coming from studies of the growth of fibroblasts on cyclically stretched substrates.…”