Dataset Information

Intrinsic remote conditioning of the myocardium as a comprehensive cardiac response to ischemia and reperfusion.

ABSTRACT: We have previously shown that distal anterior wall ischemia/reperfusion induces gene expression changes in the proximal anterior myocardial area, involving genes responsible for cardiac remodeling. Here we investigated the molecular signals of the ischemia non-affected remote lateral and posterior regions and present gene expression profiles of the entire left ventricle by using our novel and straightforward method of 2D and 3D image reconstruction. Five or 24h after repetitive 10min ischemia/reperfusion without subsequent infarction, pig hearts were explanted and myocardial samples from 52 equally distributed locations of the left ventricle were collected. Expressional changes of seven genes of interest (HIF-1?; caspase-3, transcription factor GATA4; myocyte enhancer factor 2C /MEF2c/; hexokinase 2 /HK2/; clusterin /CLU/ and excision repair cross-complementation group 4 /ERCC4/) were measured by qPCR. 2D and 3D gene expression maps were constructed by projecting the fold changes on the NOGA anatomical mapping coordinates. Caspase-3, GATA4, HK2, CLU, and ERCC4 were up-regulated region-specifically in the ischemic zone at 5 h post ischemia/reperfusion injury. Overexpression of GATA4, clusterin and ERCC4 persisted after 24 h. HK2 showed strong up-regulation in the ischemic zone and down-regulation in remote areas at 5 h, and was severely reduced in all heart regions at 24 h. These results indicate a quick onset of regulation of apoptosis-related genes, which is partially reversed in the late phase of ischemia/reperfusion cardioprotection, and highlight variations between ischemic and unaffected myocardium over time. The NOGA 2D and 3D construction system is an attractive method to visualize expressional variations in the myocardium.

SUBMITTER: Pavo N

PROVIDER: S-EPMC5620169 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Intrinsic remote conditioning of the myocardium as a comprehensive cardiac response to ischemia and reperfusion.

Pavo Noemi N Lukovic Dominika D Zlabinger Katrin K Lorant David D Goliasch Georg G Winkler Johannes J Pils Dietmar D Auer Katharina K Ankersmit Hendrik Jan HJ Giricz Zoltán Z Sárközy Márta M Jakab András A Garamvölgyi Rita R Emmert Maximilian Y MY Hoerstrup Simon P SP Hausenloy Derek J DJ Ferdinandy Péter P Maurer Gerald G Gyöngyösi Mariann M

Oncotarget 20170612 40

We have previously shown that distal anterior wall ischemia/reperfusion induces gene expression changes in the proximal anterior myocardial area, involving genes responsible for cardiac remodeling. Here we investigated the molecular signals of the ischemia non-affected remote lateral and posterior regions and present gene expression profiles of the entire left ventricle by using our novel and straightforward method of 2D and 3D image reconstruction. Five or 24h after repetitive 10min ischemia/re ...[more]

PMID: 28978029

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Project description:Toll-like receptor 2 (TLR2)-mediated myocardial inflammation serves an important role in promoting myocardial ischemic/reperfusion (I/R) injury. Previous studies have shown that miR?499 is critical for cardioprotection after ischemic postconditioning (IPostC). Therefore, the present study evaluated the protective effect of IPostC on the myocardium by inhibiting TLR2, and also assessed the involvement of microRNA (miR)?499. Rat hearts were subjected to 30 min of ischemia and 2 h of reperfusion. The IPostC was 3 cycles of 30 sec of reperfusion and 30 sec of re?occlusion prior to reperfusion. In total, 90 rats were randomly divided into six groups (n=15 per group): Sham; I/R; IPostC; miR?499 negative control adeno?associated virus (AAV) vectors + IPostC; miR?499 inhibitor AAV vectors + IPostC; and miR?499 mimic AAV vectors + IPostC. It was identified that IPostC significantly decreased the I/R?induced cardiomyocyte apoptotic index (29.4±2.03% in IPostC vs. 42.64±2.27% in I/R; P<0.05) and myocardial infarct size (48.53±2.49% in IPostC vs. 66.52±3.1% in I/R; P<0.05). Moreover, these beneficial effects were accompanied by increased miR?499 expression levels (as demonstrated by reverse transcription?quantitative PCR) in the myocardial tissue and decreased TLR2, protein kinase C (PKC), interleukin (IL)?1? and IL?6 expression levels (as demonstrated by western blotting and ELISA) in the myocardium and serum. The results indicated that IPostC + miR?499 mimics significantly inhibited inflammation and the PKC signaling pathway and enhanced the anti?inflammatory and anti?apoptotic effects of IPostC. However, IPostC + miR?499 inhibitors had the opposite effect. Therefore, it was speculated that IPostC may have a miR?499?dependent cardioprotective effect. The present results suggested that miR?499 may be involved in IPostC?mediated ischemic cardioprotection, which may occur via local and systemic TLR2 inhibition, subsequent inhibition of the PKC signaling pathway and a decrease in inflammatory cytokine release, including IL?1? and IL?6. Moreover, these effects will ultimately lead to a decrease in the myocardial apoptotic index and myocardial infarct size via the induction of the anti?apoptotic protein Bcl?2, and inhibition of the pro?apoptotic protein Bax in myocardium.

Dataset Information

Intrinsic remote conditioning of the myocardium as a comprehensive cardiac response to ischemia and reperfusion.

Publications

Intrinsic remote conditioning of the myocardium as a comprehensive cardiac response to ischemia and reperfusion.

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