HYPERLIPIDEMIA ACCELERATES ALLOGRAFT ARTERIOSCLEROSIS (CHRONIC REJECTION) IN THE RAT

The relevance of hyperlipidemia in allograft arteriosclerosis (chronic rejection) is controversial. Isolated hypercholesterolemia induced wi th cholesterol-cholic acid-diet (CC-diet) or hypertriglyceridemia indu ced 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 dou bling intimal thickness and cellularity (P<.05) but had no effect on h ost arteries. Compared with normolipidemic controls, the CC+G-diet inc reased the total serum cholesterol concentration 4.8-fold (P<.05). Lev els of VLDL, and IDL increased 4.8- and 18.1-fold (P<.05), and their c omposition changed from triglyceride-rich to cholesterol-rich lipoprot eins in an atherogenic direction. The CC+G-diet had no effect on struc ture 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 vas cular wall. Thus, elevations in VLDL and IDL lipoprotein levels and th eir cholesterol content associate with the generation of allograft art eriosclerosis 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.