Cellular mechanisms of hypertension and atherosclerosis: hypoxia-induced lipid accumulation in cultured vascular smooth muscle cells from the stroke-prone spontaneously hypertensive rat.
The effects of hypoxia on the lipid metabolism of cultured vascular smooth muscle cells from stroke-prone spontaneously hypertensive rats (SHRSP) were examined. The total cholesterol in smooth muscle cells cultured with hyperlipidaemic serum reached higher levels under hypoxic conditions (3.5% O2, 5.0% CO2, 91.5% N2) than under normal conditions (20% O2, 5.0% CO2, 75% N2). In normal serum, cholesterol increased slightly under hypoxic conditions. No difference was noted in cholesterol synthesis from [14C]-acetic acid. Triglyceride levels in smooth muscle cells cultured with hyperlipidaemic serum and normal serum were significantly increased compared with fetal calf serum. The increase in triglyceride levels was inhibited markedly under hypoxic conditions. Triglyceride synthesis induced by normal serum in the hypoxic cells was decreased compared with control cells. The metabolic rate of triglyceride did not differ between the two. These results indicate that hypoxic conditions accelerate the cellular uptake of cholesterol, an initial step in atherogenesis.
Shimizu
S
S
Hypertension-Endocrine Branch, National Institutes of Health, Bethesda, MD 20892.
Nara
Y
Y
Yamada
K
K
Keiser
H R
HR
Yamori
Y
Y
D000818:Animals; D001161:Arteriosclerosis / Q000378:metabolism*; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D050356:Lipid Metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR / Q000378:metabolism*; D011919:Rats, Inbred Strains / Q000378:metabolism*; D014280:Triglycerides / Q000378:metabolism
D014280:Triglycerides; D002784:Cholesterol