The Effects of Mechanical Stretch on Vascular Cells In Vitro: Studies of Growth and Proto-Oncogene Expression Using a New Cell-Stretching Apparatus

[摘要] Vascular hypertrophy has been identified as an important process in the development of essential hypertension. At present, the nature by which hemodynamic forces contribute to this process is poorly understood. To address the role of a hemodynamic component, the effect of a stretching force on vascular smooth muscle and endothelial cell function, was investigated. This project involved the development of an in vitro cell stretching system which satisfied the essential criteria of a sterile, cell culture system. An initial prototype was developed which vertically displaced cells grown on flexible membranes, by means of a vacuum. The surface area of the base of the dish was increased in response to suction and hence the cells attached to the base of the dish stretched. A non-uniform stretch of limited range was achieved using this system. The second prototype developed involved growing cells on silicone sheeting, mounted on a frame. Cells attached to the sheeting were stretched by increasing the length of the silicone. Due to the design of the system a fixed stretch within the range of 0-20% was achieved. 20% stretch stimulated c-fos mRNA expression and increased phosphoinositide turnover, in vsmc. However, 20% stretch did not induce c-jun or c-myc mRNA expression in vsmc. Mechanical stretch increased vsmc growth, although did not reach statistical significance. Endothelial cell studies showed that c-fos and c-jun mRNA expression was increased in response to 20% stretch. The results of these studies suggest that mechanical stretch may be an important stimulus, for the activation of signalling mechanisms, involved in vascular smooth muscle and endothelial cell growth. Therefore, such a force may play an important role in the development of vascular hypertrophy.

[发布机构] University:University of Glasgow

[关键词] Cellular biology, Developmental biology, Physiology