Cholesterol is poorly available for free apolipoprotein-mediated cellular lipid efflux from smooth muscle cells

To study the mechanism for resistance of smooth muscle cells (SMC) to cholesterol efflux caused by lipid-free apolipoproteins [Komaba, A., et al. (1992) J. Biol. Chem. 267, 17560-17566], the efflux of phospholipids and cholesterol was induced from mouse peritoneal macrophages (MP) and rat aortic SMC by phospholipid/triglyceride microemulsion, by human plasma high- and low-density lipoproteins (HDLs and LDLs), and by lipid-free human apolipoprotein (apo) A-I. The efflux of both lipids by the lipid microemulsion showed essentially the same kinetic profile for these two types of cells except that the rate of phospholipid efflux was 5-6 times slower by weight than cholesterol in both cases. The same ratio of cholesterol to phospholipid was also found in the efflux to LDLs. Lipid-free apoA-I mediated cellular cholesterol efflux, but the rate was much slower from SMC than from MP. However, the rate of apoA-I-mediated phospholipid efflux was similar between these two cells generating HDL-like particles, resulting in a high phospholipid:cholesterol ratio, (4-5):1 by weight, in the lipid efflux from SMC, in contrast with (0.8-1):1 in the lipid efflux from MP. When standardized for the cellular free cholesterol, the Vmax of cholesterol efflux induced by lipid-free apoA-I was 10 times slower from SMC than from MP, but only by at most 2-fold slower when lipid microemulsion was the acceptor. Thus, free cholesterol of SMC is less available than that of MP for free apolipoprotein-mediated generation of HDLs with cellular lipids.(ABSTRACT TRUNCATED AT 250 WORDS)