Peroxisome proliferator-activated receptor γ activators such as rosiglitazone exert beneficial metabolic effects, including improved insulin sensitivity in type 2 diabetes (T2D) management; however, recently, despite improving cardiovascular risks in preclinical models of T2D, rosiglitazone has been given a “black box” by the United States Food and Drug Administration due to increased risks of heart failure in patients with T2D. Wang et al. set out to explore possible cardiovascular risk biomarkers associated with rosiglitazone treatment in preclinical rodent models. Using vehicle/sham-operated, myocardial infarction-induced heart failure and Zucker diabetic fatty rats, these authors investigated multiple biomarkers of cardiovascular risks, including ultrasound, plasma biomarkers, pharmacogenomics profiling, and immunohistochemistry in response to clinical and supraclinical exposures of rosiglitazone. No negative effects on any of these biomarkers were detected in treated rats; in contrast, echocardiography demonstrated improved cardiac structure and function. This lack of a clear biomarker signal in Lewis rats suggests that studies in rodents might be inadequate to manifest the cardio-renal risks observed in patients. The improved cardiovascular actions observed in rodents may require further investigations to unravel the underlying mechanisms that may prove to be therapeutically beneficial.
See article at J Pharmacol Exp Ther 2010, 334:820–829.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics