Arachidonic acid-derived oxidation products initiate apoptosis in vascular smooth muscle cells

Shailaja Kalyankrishna, Jean Hugues Parmentier, Kafait Malik

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The mechanism of arachidonic acid (AA)-induced apoptosis in vascular smooth muscle cells (VSMCs) was studied in the A-10 rat aortic smooth muscle cell line. Treatment of serum-deprived VSMCs with 50μM AA for 24h resulted in a loss of cell viability. The apoptotic effect of AA was characterized by annexin V binding, sub-G1 population of cells, cell shrinkage and chromatin condensation. AA-induced VSMC death was attenuated by antioxidants alpha-tocopherol and glutathione, the hydrogen peroxide (H2O2) scavenger catalase and by serum proteins, albumin and gamma globulins. Moreover, the AA peroxidation products, 12(S)-hydroperoxyeicosatetraenoic acid (HPETE), 15(S)-HPETE, 4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA) caused VSMC apoptosis. These data suggest an oxidative mechanism of AA-induced VSMC death. The apoptotic effect of AA was pH-dependent, being inhibited by extracellular alkalinization to pH 8.0. AA inhibited serum-stimulated cell cycle progression in quiescent cells, but not in proliferating cells. In conclusion, AA, through its oxidation products causes VSMC apoptosis. Antioxidants, by inhibiting VSMC apoptosis, may prevent consequent pathological events such as atherosclerotic plaque rupture.

Original languageEnglish (US)
Pages (from-to)13-29
Number of pages17
JournalProstaglandins and Other Lipid Mediators
Volume70
Issue number1-2
DOIs
StatePublished - Sep 1 2002

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Vascular Smooth Muscle
Arachidonic Acid
Smooth Muscle Myocytes
Muscle
Cells
Apoptosis
Oxidation
Cell death
Cell Death
Antioxidants
Serum Globulins
Acids
Annexin A5
gamma-Globulins
antineoplaston A10
alpha-Tocopherol
Atherosclerotic Plaques
Malondialdehyde
Serum
Serum Albumin

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Endocrinology

Cite this

Arachidonic acid-derived oxidation products initiate apoptosis in vascular smooth muscle cells. / Kalyankrishna, Shailaja; Parmentier, Jean Hugues; Malik, Kafait.

In: Prostaglandins and Other Lipid Mediators, Vol. 70, No. 1-2, 01.09.2002, p. 13-29.

Research output: Contribution to journalArticle

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