Expression of type VIII collagen after cholesterol diet and injury in the rabbit model of atherosclerosis

This study presents an analysis of the expression of type Vm collagen mRNA in response to cholesterol diet and balloon injury in the rabbit iliac arte ry. The design of the animal experiments was as follows: 28 male New Zealan d White rabbits were divided into the 3 different treatment groups. Group 1 received regular chow; group 2 was fed with a 1% cholesterol diet for 6 we eks and normal chow for 5 weeks; and group 3 underwent balloon injury, then 6 weeks of a 1% cholesterol diet, which was followed by 5 weeks of normal chow. The expression pattern of type VIII collagen mRNA was compared with t hat of the fibrillar collagen types I and III, transforming growth factor-b eta 1, a factor known to exert the most potent stimulatory effect on collag en synthesis in vitro, and matrix metalloproteinase 1, a collagen-degrading enzyme. The cholesterol diet resulted in an upregulation of type VIII coll agen, fibrillar collagens, transforming growth factor-pi, and matrix metall oproteinase I in the adventitia. Although the number of type Vm collagen mR NA-expressing cells in the media increased, no significant difference in ov erall expression levels was detectable by northern blot analysis. The ratio of medial smooth muscle cells expressing type VIII collagen mRNA to those expressing type I and type In collagen mRNA (CVIII:CI:CIII) changed from 1: 1.88:0.03 in the normal media to 1:0.78:0.29. When cholesterol feeding was preceded by balloon injury, type VIII collagen mRNA expression concomitant with the fibrillar collagens was further upregulated over and above that le vel reported after cholesterol diet alone. In general, low levels of transf orming growth factor-beta 1 mRNA correlated with high expression of matrix metalloproteinase I. Our study indicates that a cholesterol diet resulted in a balanced reorgani zation of the collagen composition but did not result in marked collagen ac cumulation. This may provide an extracellular environment that favors migra tion and proliferation processes during early atherogenesis. It also demons trates that type VIII collagen is highly expressed and deposited at later s tages, and this may be linked to processes such as tissue reorganization du ring vascular repair and plaque stabilization.