Lipid accumulation in smooth muscle cells under LDL loading is independent of LDL receptor pathway and enhanced by hypoxic conditions

被引：38

作者：

Wada, Y

Sugiyama, A

Yamamoto, T

Naito, M

Noguchi, N

Yokoyama, S

Tsujita, M

Kawabe, Y

Kobayashi, M

Izumi, A

Kohro, T

Tanaka, T

Taniguchi, H

Koyama, H

Hirano, K

Yamashita, S

Matsuzawa, Y

Niki, E

Hamakubo, T

Kodama, T

机构：

[1] Univ Tokyo, Adv Sci & Technol Res Ctr 35, Dept Mol Biol & Med, Meguro Ku, Tokyo 1530061, Japan

[2] Univ Tokyo, Adv Sci & Technol Res Ctr, Dept Genome Sci, Tokyo 1530061, Japan

[3] Niigata Univ, Grad Sch Med & Dent Sci, Div Cellular & Mol Pathol, Niigata, Japan

[4] Nagoya City Univ, Grad Sch Med Sci, Dept Biochem Cell Biol & Metab, Nagoya, Aichi, Japan

[5] Grelan Pharmaceut Co Ltd, Res Ctr, Res & Dev, Tokyo, Japan

[6] Osaka City Univ, Grad Sch Med, Human Stress Signal Ctr, Osaka 558, Japan

[7] Osaka City Univ, Grad Sch Med, Dept Metab Endocrinol & Mol Med, Osaka 558, Japan

[8] Osaka Univ, Grad Sch Med, Dept Internal Med & Mol Sci, Osaka, Japan

[9] Chugai Pharmaceut Co Ltd, Shizuoka, Japan

来源：

ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY | 2002年 / 22卷 / 10期

关键词：

smooth muscle cells; LDL; hypoxia; cholesteryl ester;

D O I：

10.1161/01.ATV.0000033834.57737.9B

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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. Methods and 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.

引用

页码：1712 / 1719

页数：8

共 37 条

[1] EFFECT OF HYPOXIA ON UPTAKE AND DEGRADATION OF LOW-DENSITY LIPOPROTEINS BY CULTURED HUMAN ARTERIAL SMOOTH-MUSCLE CELLS [J].