title: Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions.
abstract: OBJECTIVE
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan.
authors.forename: Youichiro
authors.initials: Y
authors.lastname: Wada
authors.forename: Akira
authors.initials: A
authors.lastname: Sugiyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Makoto
authors.initials: M
authors.lastname: Naito
authors.forename: Noriko
authors.initials: N
authors.lastname: Noguchi
authors.forename: Shinji
authors.initials: S
authors.lastname: Yokoyama
authors.forename: Maki
authors.initials: M
authors.lastname: Tsujita
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Kawabe
authors.forename: Mika
authors.initials: M
authors.lastname: Kobayashi
authors.forename: Akashi
authors.initials: A
authors.lastname: Izumi
authors.forename: Takahide
authors.initials: T
authors.lastname: Kohro
authors.forename: Toshiya
authors.initials: T
authors.lastname: Tanaka
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Hidenori
authors.initials: H
authors.lastname: Koyama
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Hirano
authors.forename: Shizuya
authors.initials: S
authors.lastname: Yamashita
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Etsuo
authors.initials: E
authors.lastname: Niki
authors.forename: Takao
authors.initials: T
authors.lastname: Hamakubo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
mesh_terms: D000818:Animals; D001158:Arteries / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000473:pathology; D001345:Autoradiography; D015152:Blotting, Northern; D002250:Carbon Radioisotopes / Q000378:metabolism; D018929:Cell Culture Techniques / Q000379:methods; D015687:Cell Hypoxia; D002478:Cells, Cultured; D002784:Cholesterol / Q000096:biosynthesis / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology*; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics
chemical_list: D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D018076:DNA, Complementary; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D010100:Oxygen