Regulation of vascular smooth muscle cell growth by aldose reductase

Aruni Bhatnagar, Johannes Ruef, Si Qi Liu, Sanjay Srivastava, Satish K. Srivastava

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Aldose reductase (AR) is a broad-specificity aldo-keto reductase with wide species and tissue distribution. The enzyme has been implicated in the development of pleiotropic complications of long-term diabetes. However, the euglycemic function of the enzyme remains unclear. To examine its potential role in cell growth, changes in AR mRNA and protein were measured in human aortic smooth muscle cells exposed in culture to serum or thrombin. Stimulation by these mitogens led to an increase in the abundance of AR mRNA and protein. Furthermore, inhibition of the AR by tolrestat and sorbinil diminished DNA synthesis and cell proliferation in response to serum. Immunohistochemical staining with anti-AR antibodies revealed no significant expression of AR in the smooth muscle cells of rat carotid arteries. However, 10 and 21 days after balloon injury, intense staining was associated with the proliferating cells of the neointima. Treatment of these animals with 40 mg/kg/day sorbinil diminished the ratio of neointima to the media. Together, these observations suggest that, in vascular smooth muscle cells (VSMC), AR is a growth-responsive gene product and that inhibition of AR prevents VSMC growth and decreases intimal hyperplasia and restenosis.

Original languageEnglish (US)
Pages (from-to)627-636
Number of pages10
JournalChemico-Biological Interactions
Volume130-132
DOIs
StatePublished - Jan 30 2001

Keywords

  • Aldose reductase
  • Rat carotid artery
  • Restenosis
  • Vascular smooth muscle cells

ASJC Scopus subject areas

  • Toxicology

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    Bhatnagar, A., Ruef, J., Liu, S. Q., Srivastava, S., & Srivastava, S. K. (2001). Regulation of vascular smooth muscle cell growth by aldose reductase. Chemico-Biological Interactions, 130-132, 627-636. https://doi.org/10.1016/S0009-2797(00)00290-8