IMR Press / FBL / Volume 19 / Issue 3 / DOI: 10.2741/4227

Frontiers in Bioscience-Landmark (FBL) is published by IMR Press from Volume 26 Issue 5 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Pharmacological postconditioning treatment of myocardial infarction with netrin-1
Show Less
1 Divisions of Molecular Medicine and Cardiology, Departments of Anesthesiology and Medicine, Cardiovascular Research Laboratories, David Geffen School of Medicine at University of California Los Angeles, 650 Charles E. Young Drive, Los Angeles, CA 90095, USA
Academic Editor:Xiao-Feng Yang
Front. Biosci. (Landmark Ed) 2014, 19(3), 566–570; https://doi.org/10.2741/4227
Published: 1 January 2014
(This article belongs to the Special Issue CREG promotes vasculogenesis by activation of VEGFPI3KAkt pathway)
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.

Keywords
Netrin-1
Pharmacological postconditioning
Cardioprotection
Ischemia reperfusion (I/R) injury
deleted in colorectal cancer (DCC)
ERK1/2
nitric oxide (NO)
Share
Back to top