HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Srivastava, S. Articles by Bhatnagar, A. Search for Related Content PubMed PubMed Citation Articles by Srivastava, S. Articles by Bhatnagar, A. Social Bookmarking                What's this?

Contribution of Aldose Reductase to Diabetic Hyperproliferation of Vascular Smooth Muscle Cells

¹ Institute of Molecular Cardiology, Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky
² Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas

Address correspondence and reprint requests to Sanjay Srivastava, PhD, Division of Cardiology, Department of Medicine, Delia Baxter Building, 580 S. Preston St., Room 421B, University of Louisville, Louisville, KY 40202. E-mail: sanjay{at}louisville.edu

Abbreviations: DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; HNE, 4-hydroxy trans 2-nonenal; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide; PCNA, proliferative cell nuclear antigen; PKC, protein kinase C; SMC, smooth muscle cell; STZ, streptozotocin; VSMC, vascular SMC

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-G₁ 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.

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. Pladzyk, A. B. M. Reddy, U. C. S. Yadav, R. Tammali, K. V. Ramana, and S. K. Srivastava Inhibition of Aldose Reductase Prevents Lipopolysaccharide-Induced Inflammatory Response in Human Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5395 - 5403. [Abstract] [Full Text] [PDF]

				K. V. Ramana, A. A. Fadl, R. Tammali, A. B. M. Reddy, A. K. Chopra, and S. K. Srivastava Aldose Reductase Mediates the Lipopolysaccharide-induced Release of Inflammatory Mediators in RAW264.7 Murine Macrophages J. Biol. Chem., November 3, 2006; 281(44): 33019 - 33029. [Abstract] [Full Text] [PDF]