Hyperlipidemia accelerates allograft arteriosclerosis (chronic rejection) in the rat

The relevance of hyperlipidemia in allograft arteriosclerosis (chronic rejection) is controversial. Isolated hypercholesterolemia induced with cholesterol-cholic acid-diet (CC-diet) or hypertriglyceridemia induced with glycerol-diet (G-diet) had no or only a protective effect on aortic allograft arteriosclerosis in the rat. Combined hyperlipidemia with both diets (CC+G-diet) enhanced allograft arteriosclerosis by doubling intimal thickness and cellularity (P < .05) but had no effect on host arteries. Compared with normolipidemic controls, the CC+G-diet increased the total serum cholesterol concentration 4.8-fold (P < .05). Levels of VLDL2 and IDL increased 4.8- and 18.1-fold (P < .05), and their composition changed from triglyceride-rich to cholesterol-rich lipoproteins in an atherogenic direction. The CC+G-diet had no effect on the structure of inflammation in the vascular wall. Instead, significant lipid deposits were observed, and the expression of epidermal growth factor and insulin-like growth factor-1 was significantly elevated in the vascular wall. Thus, elevations in VLDL and IDL lipoprotein levels and their cholesterol content associate with the generation of allograft arteriosclerosis in rats. Deposition of lipids in the vascular wall seems to induce local synthesis of certain growth factors, which ultimately leads to the induction of smooth muscle cell replication.