Metabolism of cholesterol and phospholipids in cultured human vascular smooth muscle cells: Differences between artery and vein-derived cells and the effect of oxygen partial pressure

Human smooth muscle (SM) cells derived from vena saphena magna, aorta abdominalis and arteria mamaria were grown in culture under 40 or 145 mmHg oxygen partial pressure (pO₂) and their lipid metabolism studied. Esterification of the cellular [³H]cholesterol was higher by 2.5-fold in artery derived than in vein-derived cells and was slightly higher in cultures exposed to 145 mm Hg than to 40 mm Hg pO₂. Cholesterol efflux in the presence of high density lipoprotein (HDL) in the incubation medium was higher in artery-derived than vein-derived cells. Apolipoprotein (apo) AI also supported cholesterol efflux to a higher extent in artery than in vein-derived cells. Cholesterol efflux in the presence of apo AI was accompanied by a decrease of 50% in cellular [³H]cholesteryl ester in both cell types. SM cultures exposed to [³H]choline incorporated about 90% of the radioactivity to phosphatidylcholine (PC) and 10% to sphingomyelin (SPM). During 5 days exposure to [³H[choline, 10 to 15% and 20 to 30% of the newly synthesized PC and SPM, respectively, were released by vein-derived cells into the incubation medium. The relative amount of SPM of the total radioactive phospholipids released by vein-derived cultures was significantly higher in cultures growing under 40 mm Hg than 145 mm Hg pO₂ reaching a value of up to 33% of the radioactive phospholipids in the incubation medium. HDL was shown to serve as an acceptor for phospholipids released by both vein and artery-derived SM cells, while free apo AI supported phospholipid efflux in artery but not in vein-derived SM cells. This study demonstrates higher cholesterol esterification in artery than vein-derived SM cells. Furthermore, lipid metabolism in vein derived SM cells is affected by the oxygen partial pressure so that cholesterol esterification is lower and SPM efflux is higher at 40 mm Hg than at 145 mm Hg pO₂. These results may suggest differences between artery and vein-derived SM cells, and a role for the oxygen partial pressure in lipid metabolism which correlates with the higher frequency of atherosclerosis in arteries than in veins.