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Acute Rosiglitazone Treatment is Cardioprotective against Ischemia/Reperfusion Injury by Modulating AMPK, Akt, and JNK Signaling in Non-diabetic Mice.
MedLine Citation:
PMID:  21666107     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Rosiglitazone (RGZ), a PPAR-γ agonist, has been demonstrated to possess cardioprotective properties during ischemia/reperfusion (I/R). However, this notion remains controversial as recent evidence has suggested an increased risk in cardiac events associated with long-term use of RGZ in patients with type 2 diabetes. In this study, we tested the hypothesis that acute RGZ treatment is beneficial during I/R by modulating cardioprotective signaling pathways in a non-diabetic mouse model. RGZ (1 µg/g) was injected intravenously (i.v.) via tail vein 5 min before reperfusion. Myocardial infarction was significantly reduced in mice treated with RGZ compared to vehicle controls (8.7% ± 1.1% vs. 20.2% ± 2.5%, P<0.05). Moreover, isolated hearts were subjected to 20 min of global, no-flow ischemia in an ex vivo heart perfusion system. Post-ischemic recovery was significantly improved with RGZ treatment administered at the onset of reperfusion compared to vehicle (P<0.001). The immunoblotting data revealed that the levels of both p-AMPK (Thr(172)) and p-Akt (Ser(473)) were significantly up-regulated when RGZ was administered 5 min before reperfusion compared to vehicle. On the other hand, inflammatory signaling, p-JNK (Thr(183)/Tyr(185)), was significantly down-regulated as a result of RGZ treatment compared to vehicle (P<0.05). Intriguingly, pre-treatment with the selective PPAR-γ inhibitor GW-9662 (1 µg/g, i.v.) 10 min before reperfusion significantly attenuated these beneficial effects of RGZ on the ischemic heart. Taken together, acute treatment with RGZ can reduce ischemic injury in a non-diabetic mouse heart via modulating AMPK, Akt, and JNK signaling pathways that is dependent upon PPAR-γ activation.
Authors:
Alex Morrison; Xiaoyan Yan; Chao Tong; Ji Li
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-10
Journal Detail:
Title:  American journal of physiology. Heart and circulatory physiology     Volume:  -     ISSN:  1522-1539     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901228     Medline TA:  Am J Physiol Heart Circ Physiol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
1University at Buffalo-SUNY.
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