Inhibitory activity of clinical thiazolidinedione peroxisome proliferator activating receptor-gamma ligands toward internal mammary artery, radial artery, and saphenous vein smooth muscle cell proliferation.
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-gamma (PPARgamma) 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.


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>rosiglitazone approximately pioglitazone, and this potency profile was maintained toward the growth factor and insulin-stimulated phosphorylation of the retinoblastoma protein, which controls cell cycle progression.


CONCLUSIONS
The inhibitory potency of clinical thiazolidinediones toward different vascular sources is dependent on the individual thiazolidinedione and very little on the vascular source.
Cell Biology of Diabetes, Baker Heart Research Institute, Commercial Rd, PO Box 6492, St Kilda Rd, Central, Melbourne, Victoria 8008, Australia.
Stephanie T
ST
de Dios
Dennis
D
Bruemmer
Rodney J
RJ
Dilley
Melanie E
ME
Ivey
Garry L R
GL
Jennings
Ronald E
RE
Law
Peter J
PJ
Little
D000077214:Becaplermin; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000378:metabolism / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008024:Ligands; D008323:Mammary Arteries / Q000166:cytology; D008934:Mitogens / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D000077205:Pioglitazone; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D017534:Radial Artery / Q000166:cytology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000378:metabolism; D000077154:Rosiglitazone; D012501:Saphenous Vein / Q000166:cytology; D013844:Thiazoles / Q000378:metabolism / Q000494:pharmacology*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D007328:Insulin; D008024:Ligands; D008934:Mitogens; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D018160:Receptors, Cytoplasmic and Nuclear; D016160:Retinoblastoma Protein; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone; D000077214:Becaplermin; D000077288:Troglitazone; D000077205:Pioglitazone