Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression

Rao Gadiparthi, Bradford C. Berk

Research output: Contribution to journalArticle

539 Citations (Scopus)

Abstract

Vascular smooth muscle cells (VSMCs) proliferate in response to arterial injury. Recent findings suggest that, in addition to platelet-derived growth factors, growth factors from inflammatory cells and endothelial cells at the site of injury may contribute to VSMC proliferation. We hypothesized that a common mechanism by which endothelial cells and inflammatory cells stimulate VSMC growth could be the active oxygen species (i.e., O2-, H2O2, and .OH) generated during arterial injury. Using xanthine/ xanthine oxidase to generate active oxygen species, we studied the effects of these agents on VSMC growth. Xanthine/xanthine oxidase (100 μM xanthine and 5 microunits/ml xanthine oxidase) stimulated DNA synthesis in growth-arrested VSMCs by 180% over untreated cells. Administration of the scavenging enzymes superoxide dismutase and catalase demonstrated that H2O2 was primarily responsible for xanthine/xanthine oxidase-induced VSMC DNA synthesis. H2O2 directly increased VSMC DNA synthesis and cell number (maximal at 200 μM) but decreased DNA synthesis of endothelial cells and ftbroblasts. This effect was protein kinase C independent: sphingosine, a potent protein kinase C inhibitor, failed to block H2O2-induced VSMC DNA synthesis. H2O2 (200 μM) stimulated c-myc and c-fos mRNA levels by fourfold and 20-fold, respectively, as compared with quiescent levels. In contrast to DNA synthesis, H2O2 induction of c-myc and c-fos mRNA was primarily protein kinase C dependent. These findings show that H2O2 specifically increases VSMC DNA synthesis and suggest a role for this oxidant in intimal proliferation, especially after arterial injury.

Original languageEnglish (US)
Pages (from-to)593-599
Number of pages7
JournalCirculation Research
Volume70
Issue number3
StatePublished - 1990
Externally publishedYes

Fingerprint

Proto-Oncogenes
Vascular Smooth Muscle
Smooth Muscle Myocytes
Reactive Oxygen Species
Xanthine
Growth
Xanthine Oxidase
DNA
Protein Kinase C
Endothelial Cells
Wounds and Injuries
Tunica Intima
Messenger RNA
Sphingosine
Protein C Inhibitor
Platelet-Derived Growth Factor
Protein Kinase Inhibitors
Oxidants
Catalase
Superoxide Dismutase

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Active oxygen species stimulate vascular smooth muscle cell growth and proto-oncogene expression. / Gadiparthi, Rao; Berk, Bradford C.

In: Circulation Research, Vol. 70, No. 3, 1990, p. 593-599.

Research output: Contribution to journalArticle

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