Wada Youichiro, Sugiyama Akira, Yamamoto Takashi, Naito Makoto, Noguchi Noriko, Yokoyama Shinji, Tsujita Maki, Kawabe Yoshiki, Kobayashi Mika, Izumi Akashi, Kohro Takahide, Tanaka Toshiya, Taniguchi Hirokazu, Koyama Hidenori, Hirano Ken-ichi, Yamashita Shizuya, Matsuzawa Yuji, Niki Etsuo, Hamakubo Takao, Kodama Tatsuhiko
Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan.
Arterioscler Thromb Vasc Biol. 2002 Oct 1;22(10):1712-9. doi: 10.1161/01.atv.0000033834.57737.9b.
The effect of a variety of hypoxic conditions on lipid accumulation in smooth muscle cells (SMCs) was studied in an arterial wall coculture and monocultivation model.
Low density lipoprotein (LDL) was loaded under various levels of oxygen tension. Oil red O staining of rabbit and human SMCs revealed that lipid accumulation was greater under lower oxygen tension. Cholesterol esters were shown to accumulate in an oxygen tension-dependent manner by high-performance liquid chromatographic analysis. Autoradiograms using radiolabeled LDL indicated that LDL uptake was more pronounced under hypoxia. This result holds in the case of LDL receptor-deficient rabbit SMCs. However, cholesterol biosynthesis and cellular cholesterol release were unaffected by oxygen tension.
Hypoxia significantly increases LDL uptake and enhances lipid accumulation in arterial SMCs, exclusive of LDL receptor activity. Although the molecular mechanism is not clear, the model is useful for studying lipid accumulation in arterial wall cells and the difficult-to-elucidate events in the initial stage of atherogenesis.
