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This Article Full Text Full Text (PDF) All Versions of this Article: 287/5/C1273    most recent 00230.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by Ragolia, L. Articles by Maesaka, J. K. Search for Related Content PubMed PubMed Citation Articles by Ragolia, L. Articles by Maesaka, J. K.

VASCULAR BIOLOGY

Inhibition of cell cycle progression and migration of vascular smooth muscle cells by prostaglandin D₂ synthase: resistance in diabetic Goto-Kakizaki rats

¹Vascular Biology Laboratory, Winthrop-University Hospital, Mineola 11501; and the ²Stony Brook University School of Medicine, Stony Brook, New York 11794

Submitted 11 May 2004 ; accepted in final form 1 July 2004

The regulation of vascular smooth muscle cell (VSMC) proliferation, migration, and apoptosis plays a clear role in the atherosclerotic process. Recently, we reported on the inhibition of the exaggerated growth phenotype of VSMCs isolated from hypertensive rats by lipocalin-type prostaglandin D₂ synthase (L-PGDS). In the present study, we report the differential effects of L-PGDS on VSMC cell cycle progression, migration, and apoptosis in wild-type VSMCs vs. those from a type 2 diabetic model. In wild-type VSMCs, exogenously added L-PGDS delayed serum-induced cell cycle progression from the G₁ to S phase, as determined by gene array analysis and the decreased protein expressions of cyclin-dependent kinase-2, p21^Cip1, and cyclin D1. Cyclin D3 protein expression was unaffected by L-PGDS, although its gene expression was stimulated by L-PGDS in wild-type cells. In addition, platelet-derived growth factor-induced VSMC migration was inhibited by L-PGDS in wild-type cells. Type 2 diabetic VSMCs, however, were resistant to the L-PGDS effects on cell cycle progression and migration. L-PGDS did suppress the hyperproliferation of diabetic cells, albeit through a different mechanism, presumably involving the 2.5-fold increase in apoptosis and the concomitant 10-fold increase of L-PGDS uptake we observed in these cells. We propose that in wild-type VSMCs, L-PGDS retards cell cycle progression and migration, precluding hyperplasia of the tunica media, and that diabetic cells appear resistant to the inhibitory effects of L-PGDS, which consequently may help explain the increased atherosclerosis observed in diabetes.

apoptosis; atherosclerosis; insulin resistance

This article has been cited by other articles:

				J. H. Lee, T. Palaia, and L. Ragolia Impaired insulin-mediated vasorelaxation in diabetic Goto-Kakizaki rats is caused by impaired Akt phosphorylation Am J Physiol Cell Physiol, February 1, 2009; 296(2): C327 - C338. [Abstract] [Full Text] [PDF]