Pharmacological postconditioning treatment of myocardial infarction with netrin-1.
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| Abstract |
The present study investigated whether pharmacological postconditoning with netrin-1 is cardioprotective against ischemia reperfusion (I/R) injury, and the underlying signaling mechanisms. Langendorff perfused hearts isolated from wild-type (WT) C57BL/6 or DCC+/- mice underwent a 20-min of ischemia, followed by a 60-min of reperfusion, in the presence or absence of netrin-1, or netrin-1 in combination with U0126 (MEK1/2 inhibitor), or PTIO (nitric oxide/NO scavenger). In WT mice, netrin-1 postconditioning dramatically reduced infarct size to 17.0±2.5%, from 40.5±4.2% in the untreated I/R group. U0126 or PTIO alone had no effect on infarct size but abolished the effects of netrin-1. The protective effect of netrin-1 was markedly diminished in DCC+/- mice (44.5±2% vs. 15±2.6 % for infract size in DCC+/- vs. DCC+/+ group). Our results indicate that netrin-1, given as a pharmacological postconditioning agent, induces cardioprotection via a DCC-dependent mechanism that involves ERK1/2 activation and NO production. Combined with our previous findings, netrin-1 treatment proves to be extremely and consistently beneficial whenever delivered to the heart, establishing its substantial promises for being developed into a robust therapeutic strategy for acute myocardial infarction.
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| Authors | Jalaleddinne Omar Bouhidel, Ping Wang, Qiang Li, Hua Cai |
| Journal | Frontiers in bioscience (Landmark edition) (Front Biosci (Landmark Ed)) Vol. 19 Issue 3 Pg. 566-70 (01 01 2014) ISSN: 2768-6698 [Electronic] Singapore |
| PMID | 24389204 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't) |
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