LIPID BIOSYNTHESIS IN CULTURED ARTERIAL SMOOTH-MUSCLE CELLS IS RELATED TO THEIR PHENOTYPE

During the atherogenic process in vivo, arterial smooth muscle cells ( SMC) undergo changes in their phenotype. In the present study, rat SMC from primary cultures and from subcultures before 10 and after 200 pa ssages, showing contractile-like, synthetic and transformed phenotypes , respectively, were compared in regard to their lipid content and bio synthesis. The rationale for comparing these phenotypes rests in the s imilar changes in phenotype of SMC that occur in the formation and pro gression of atherosclerotic lesions. Phenotype changes were shown to b e associated with changes in the phospholipid content of SMC. Phosphol ipid levels increased, but not as significantly as did cholesterol lev els when passing from contractile to synthetic and transformed cells ( 1.23 +/- 0.18, 2.28 +/- 0.26 and 3.25 +/- 0.23 mug/10(6) cells, respec tively). Cholesterol normalized in respect to cell protein was increas ed to the same extent. Lipid synthesis as judged by [C-14]acetate inco rporation was increased 3- to 12-fold in the synthetic and transformed cells, respectively, compared to contractile cells. After thin-layer chromatography, radioactivity was shown to be markedly increased in mo st of the lipid fractions, but label in the cholesterol fraction of sy nthetic and transformed cells was increased by 7- and 21-fold, respect ively. Thus, SMC in vitro were shown to drastically increase cholester ol biosynthesis associated with phenotype changes. Such changes are kn own to occur in vivo and might represent a critical step in the deposi tion of excess cholesterol within foam cells.