Vascular effects of TZDs: new implications.
The incidence of diabetes, now affecting more than 170 million individuals is growing rapidly. Type 2 diabetes, which accounts for 90% of all diabetes cases, is associated with increased cardiovascular morbidity and mortality. Thiazolidinediones (TZDs), used for the treatment of patients with type 2 diabetes improve insulin sensitivity and endothelial dysfunction and exert beneficial effects on the lipid profile by activating the peroxisome proliferator-activated receptor gamma (PPAR-gamma). Moreover, a large body of evidence indicates that TZDs exhibit antiatherogenic effects independent of their antidiabetic and lipid-lowering properties by modulating inflammatory processes. This review will focus on the role of PPAR-gamma agonists in the vessel wall and summarize their effects on C-reactive protein (CRP), plasminogen activator inhibitor type-1 (PAI-1), matrix metalloproteinase-9 (MMP-9), adiponectin and ATP-binding cassette transporter A1 (ABCA1) and their implications for treatment of advanced stages of atherosclerosis, particularly in a setting of type 2 diabetes.
Blaschke
Florian
F
Division of Endocrinology, Diabetes and Hypertension, David Geffen School of Medicine, University of California, Los Angeles, CA 90095, USA.
Spanheimer
Robert
R
Khan
Mehmood
M
Law
Ronald E
RE
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D050197:Atherosclerosis / Q000150:complications / Q000188:drug therapy; D002097:C-Reactive Protein / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists* / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D052242:Adiponectin; D007004:Hypoglycemic Agents; D047495:PPAR gamma; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; D002097:C-Reactive Protein; D020780:Matrix Metalloproteinase 9