Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells

Sanjay Srivastava, Kota Ramana, Ravinder Tammali, Satish Srivastava, Aruni Bhatnagar

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The objective of this study was to determine whether the polyol pathway enzyme aldose reductase mediates diabetes abnormalities in vascular smooth muscle cell (SMC) growth. Aldose reductase inhibitors (tolrestat or sorbinil) or antisense aldose reductase mRNA prevented hyperproliferation of cultured rat aortic SMCs induced by high glucose. Cell cycle progression in the presence of high glucose was blocked by tolrestat, which induced a G0-G 1 phase growth arrest. In situ, diabetes increased SMC growth and intimal hyperplasia in balloon-injured carotid arteries of streptozotocin- treated rats, when examined 7 or 14 days after injury. Treatment with tolrestat (15 mg·kg-1·day-1) diminished intimal hyperplasia and decreased SMC content of the lesion by 25%. Although tolrestat treatment increased immunoreactivity of the lesion with antibodies raised against protein adducts of the lipid peroxidation product 4-hydroxy trans-2-nonenal, no compensatory increase in lesion fibrosis was observed. Collectively, these results suggest that inhibition of aldose reductase prevents glucose-induced stimulation of SMC growth in culture and in situ. Even though inhibition of aldose reductase increases vascular oxidative stress, this approach may be useful in preventing abnormal SMC growth in vessels of diabetic patients.

Original languageEnglish (US)
Pages (from-to)901-910
Number of pages10
JournalDiabetes
Volume55
Issue number4
DOIs
StatePublished - 2006

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Aldehyde Reductase
Vascular Smooth Muscle
Smooth Muscle Myocytes
Tunica Intima
Growth
Glucose
Hyperplasia
Streptozocin
Carotid Arteries
Lipid Peroxidation
Blood Vessels
Cell Cycle
Oxidative Stress
Fibrosis
Messenger RNA
tolrestat
Antibodies
Wounds and Injuries
Enzymes
Therapeutics

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells. / Srivastava, Sanjay; Ramana, Kota; Tammali, Ravinder; Srivastava, Satish; Bhatnagar, Aruni.

In: Diabetes, Vol. 55, No. 4, 2006, p. 901-910.

Research output: Contribution to journalArticle

Srivastava, Sanjay ; Ramana, Kota ; Tammali, Ravinder ; Srivastava, Satish ; Bhatnagar, Aruni. / Contribution of aldose reductase to diabetic hyperproliferation of vascular smooth muscle cells. In: Diabetes. 2006 ; Vol. 55, No. 4. pp. 901-910.
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