Netrin-1 improves post-injury cardiac function in vivo via DCC/NO-dependent preservation of mitochondrial integrity, while attenuating autophagy.

ABSTRACT: Reperfusion injury of the heart is a severe complication of angioplasty treatment of acute myocardial ischemia, for which no therapeutics are currently available. The present study aimed to identify whether and how a novel protein, netrin-1, induces cardioprotection in vivo during ischemia/reperfusion (I/R) injury. Wild type (WT) C57BL6/J mice were subjected to a 30 min coronary occlusion followed by a 24h reperfusion with vehicle (normal saline), netrin-1, UO126 (MEK1/2 inhibitor), PTIO (nitric oxide/NO scavenger), netrin-1/UO126 or netrin-1/PTIO intraventricularly. Some were injected of netrin-1 via tail vein. Netrin-1 at 5μg/kg induced a substantial reduction in infarct size (19.7 ± 5.0% from 41.3 ± 1.8% in the controls), and markedly improved cardiac function as measured by ejection fr

SUBMITTER: Bouhidel JO 

PROVIDER: S-EPMC4262720 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature