Rosiglitazone is cardioprotective in a murine model of myocardial I/R.
The peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a regulator of anti-inflammatory genes. One of its agonists, rosiglitazone-widely used in the treatment of type 2 diabetes mellitus-has recently been reported to increase the risk for myocardial infarction. In contrast, various studies provide evidence for a rosiglitazone-induced cardioprotection in different models of acute myocardial I/R. Here, we report that this protection can still be observed after 28 days of reperfusion in a murine model even when treatment commenced after the period of ischemia (reperfusion therapy). In vitro, cells from the rat cardiomyoblast cell line H9c2(2-1) are protected against oxidative stress by incubation with rosiglitazone, which can be abrogated by dexamethasone or cycloheximide. The antioxidant enzyme heme oxygenase 1 is up-regulated in these cells after rosiglitazone treatment. Our data provide further evidence that rosiglitazone exerts protective effects during myocardial I/R and might contribute to the reevaluation of the approved drug rosiglitazone.
Department of Anaesthesia, University Hospital Dusseldorf, Dusseldorf, Germany.
Jan
J
Mersmann
Nguyen
N
Tran
Paula A
PA
Zacharowski
Dirk
D
Grotemeyer
Kai
K
Zacharowski
D000818:Animals; D002460:Cell Line; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000517:prevention & control; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*
D045162:Thiazolidinediones; D000077154:Rosiglitazone; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat