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Cytotoxicity of some oxysterols on human vascular smooth muscle cells was mediated by apoptosis

Y Miyashita1, K Shirai, Y Ito

  • 1Sakura Hospital, Toho University School of Medicine, Chiba, Japan.

Journal of Atherosclerosis and Thrombosis
|January 1, 1997
PubMed

Insights

Oxysterols like 7-ketocholesterol and 7 beta-hydroxycholesterol induce cell death in vascular smooth muscle cells. This cytotoxicity, observed in advanced atherosclerosis, is mediated by apoptosis, a programmed cell death pathway.

Area of Science:

  • Cardiovascular Biology
  • Cellular Toxicology
  • Lipid Metabolism

Background:

  • Vascular smooth muscle cell (VSMC) loss is a hallmark of advanced atherosclerotic lesions.
  • Oxysterols, derived from cholesterol oxidation, are implicated as potentially toxic lipids in atherosclerosis.

Purpose of the Study:

  • To investigate the cytotoxic effects of specific oxysterols on human VSMCs.
  • To elucidate the mechanism of cell death induced by these oxysterols.

Main Methods:

  • Human VSMCs were treated with 7-ketocholesterol and 7 beta-hydroxycholesterol.
  • Cell detachment, DNA fragmentation (TUNEL assay, agarose gel electrophoresis), and lactate dehydrogenase release were measured.

Main Results:

  • Oxysterol treatment significantly increased VSMC detachment in a dose-dependent manner.
  • DNA nicking and fragmentation, indicative of apoptosis, were observed.
  • Lactate dehydrogenase release, a marker of cell membrane damage, increased following DNA fragmentation.

Conclusions:

  • 7-ketocholesterol and 7 beta-hydroxycholesterol exhibit significant cytotoxicity towards human VSMCs.
  • The mechanism of oxysterol-induced VSMC death involves apoptosis.

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