Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions.
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.
Wada
Youichiro
Y
Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology, University of Tokyo, Japan.
Sugiyama
Akira
A
Yamamoto
Takashi
T
Naito
Makoto
M
Noguchi
Noriko
N
Yokoyama
Shinji
S
Tsujita
Maki
M
Kawabe
Yoshiki
Y
Kobayashi
Mika
M
Izumi
Akashi
A
Kohro
Takahide
T
Tanaka
Toshiya
T
Taniguchi
Hirokazu
H
Koyama
Hidenori
H
Hirano
Ken-ichi
K
Yamashita
Shizuya
S
Matsuzawa
Yuji
Y
Niki
Etsuo
E
Hamakubo
Takao
T
Kodama
Tatsuhiko
T
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
D002250:Carbon Radioisotopes; D002788:Cholesterol Esters; D018076:DNA, Complementary; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D010100:Oxygen