Resistance of smooth muscle cells to assembly of high density lipoproteins with extracellular free apolipoproteins and to reduction of intracellularly accumulated cholesterol.
Removal of intracellularly accumulated cholesterol by lipid-free human apolipoproteins (apo) A-I and A-II was studied for aortic smooth muscle cells (SMC) of rat, monkey and rabbit, human skin fibroblasts (FB), and mouse peritoneal macrophages (MP). The reaction generated high density lipoprotein (HDL)-like lipoproteins as did those and other helical apolipoproteins with MP, causing efflux of cellular cholesterol. From FB and MP, the maximum efflux rates with apoA-I and A-II per 24 h were as much as 30% of the apparent maximum efflux rate of prelabeled cellular cholesterol to human HDL. From rat SMC these rates were 7.2 and 6.8%, respectively, being independent of cellular cholesterol content. Those from monkey and rabbit SMC were also very low. When standardized for the initial cellular unesterified cholesterol pool size, the maximum efflux rates/24 h were 5.4 and 5.0% for apoA-I and A-II from rat SMC and even less from monkey and rabbit SMC in contrast to 42.4 and 39.7% from FB, and 53.0 and 45.5% from MP, respectively. The standardized apparent maximum efflux to HDL was 76% from rat SMC, 45 and 31% from monkey and rabbit SMC, 139% from FB and 166% from MP. Accordingly, the reaction with free apolipoproteins caused significant net reduction of cellular cholesterol, predominantly in cholesteryl ester, in FB and MP, but not in SMC. While the efflux Km with apoA-I and A-II were 7.5 and 4.5 micrograms/ml for MP, those for SMC and FB were both 1 microgram/ml or lower, as low as 1/1500 and 1/500 of their plasma concentrations, respectively. The apparent efflux Km for HDL were, on the other hand, all in the range of 36 to 65 micrograms of protein/ml for SMC, FB, and MP, showing that the mode of cholesterol exchange of these cells with lipoprotein surface is not significantly different from each other. Thus, peripheral cells such as FB may provide a significant source of HDL by interacting with extracellular free apolipoproteins in interstitial fluid, reducing intracellularly accumulated cholesterol. However, SMC seem very resistant to this interaction, suggesting that atheromatous lesions predominantly consisting of SMC are resistant to regression.
Komaba
A
A
Department of Medicine, University of Alberta, Edmonton, Canada.
Li
Q
Q
Hara
H
H
Yokoyama
S
S
D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D016632:Apolipoprotein A-I / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000378:metabolism; D001057:Apolipoproteins E / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D000882:Haplorhini; D006801:Humans; D007700:Kinetics; D008075:Lipoproteins, HDL / Q000097:blood / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000378:metabolism
D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001057:Apolipoproteins E; D002788:Cholesterol Esters; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; C014409:cholesteryl oleate; D002784:Cholesterol