Direct attenuation of plasminogen activator inhibitor type-1 expression in human adipose tissue by thiazolidinediones.
Adipose tissue produces substantial amounts of plasminogen activator inhibitor type-1 (PAI-1), an established cardiovascular risk factor. This study evaluated PAI-1 expression in human adipose tissue in response to thiazolidinediones, insulin sensitising drugs activating peroxisome proliferator-activated receptor-gamma (PPAR-gamma). Troglitazone, rosiglitazone, and ciglitazone significantly reduced PAI-1 protein expression in human preadipocytes under basal conditions and after stimulation of the cells with TGF-beta. Pioglitazone had no effect. In human adipocytes all four thiazolidinediones significantly attenuated PAI-1 expression. Signalling appeared to be mediated via PPAR-gamma and effects reflected, at least in part, changes in transcription. Accordingly, patients with insulin resistance may benefit from treatment with thiazolidinediones with respect to diminution of PAI-1 expression in adipose tissue and consequent potential reduction of cardiovascular risk.
Zirlik
Andreas
A
Brigham and Women's Hospital, Harvard Medical School, Cardiovascular Medicine, Department of Medicine, Boston, Massachusetts 02115, USA. azirlik@aol.com
Leugers
Anne
A
Lohrmann
Jens
J
Ernst
Sandra
S
Sobel
Burton E
BE
Bode
Christoph
C
Nordt
Thomas K
TK
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007333:Insulin Resistance; D047495:PPAR gamma / Q000378:metabolism; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000096:biosynthesis*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology*; D014158:Transcription, Genetic; D000077288:Troglitazone
D002839:Chromans; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077288:Troglitazone; C039671:ciglitazone; D000077205:Pioglitazone