Published Online
on May 12, 2003

A more recent version of this article appeared on May 27, 2003

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Submitted on February 5, 2003
Revised on April 10, 2003
Accepted on April 11, 2003

Inhibitory Activity of Clinical Thiazolidinedione Peroxisome Proliferator Activating Receptor- Ligands Toward Internal Mammary Artery, Radial Artery, and Saphenous Vein Smooth Muscle Cell Proliferation

Stephanie T. de Dios BAppSC(Hons), Dennis Bruemmer MD, Rodney J. Dilley PhD, Melanie E. Ivey BAppSci, Garry L.R. Jennings MBBS, PhD, Ronald E. Law PhD, and Peter J. Little PhD^*

From the Cell Biology of Diabetes (S.T.d.D., M.E.I., G.L.R.J., P.J.L.) and Morphology Laboratories (R.J.D.), Baker Heart Research Institute, Melbourne, Victoria, Australia; Monash University (S.T.d.D., G.L.R.J., P.J.L.), Department of Medicine, Melbourne, Victoria, Australia; and the Division of Endocrinology (D.B., R.E.L.), Diabetes and Hypertension, UCLA, Los Angeles, Calif.

^* To whom correspondence should be addressed. E-mail: peter.little{at}baker.edu.au.

Background--The proliferation of vascular smooth muscle cells (VSMCs) is a known response to arterial injury that is an important part of the process of restenosis and atherosclerosis. People with diabetes have an increased risk of cardiovascular disease resulting from accelerated coronary atherosclerosis. The newest drugs for Type 2 diabetes are thiazolidinediones, which are insulin-sensitizing peroxisome proliferator activating receptor- (PPAR) ligands. We investigated the antiproliferative effects of troglitazone, rosiglitazone, and pioglitazone on VSMCs derived from the three vascular beds used for coronary artery by-pass grafting: the internal mammary and radial artery and saphenous veins.

Methods and Results--The three vessels yielded proliferating cells of slightly differing morphology. Inhibition of cell proliferation was assessed by cell counting and cell cycle studies by Western blotting for phosphorylated retinoblastoma protein. All three thiazolidinediones showed inhibitory potency toward cell proliferation with a potency troglitazone>rosiglitazonepioglitazone, and this potency profile was maintained toward the growth factor and insulin-stimulated phosphorylation of the retinoblastoma protein, which controls cell cycle progression.

Conclusion--The inhibitory potency of clinical thiazolidinediones toward different vascular sources is dependent on the individual thiazolidinedione and very little on the vascular source.

Key words: muscle, smooth • diabetes mellitus • restenosis • grafting

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