Different signalling in infarcted and non-infarcted areas of rat failing hearts: A role of necroptosis and inflammation

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67985823%3A_____%2F19%3A00510386" target="_blank" >RIV/67985823:_____/19:00510386 - isvavai.cz</a>

Result on the web

<a href="https://doi.org/10.1111/jcmm.14536" target="_blank" >https://doi.org/10.1111/jcmm.14536</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1111/jcmm.14536" target="_blank" >10.1111/jcmm.14536</a>

Result language

angličtina

Original language name

Different signalling in infarcted and non-infarcted areas of rat failing hearts: A role of necroptosis and inflammation

Original language description

Necroptosis has been recognized in heart failure (HF). In this study, we investigated detailed necroptotic signalling in infarcted and non-infarcted areas separately and its mechanistic link with main features of HF. Post-infarction HF in rats was induced by left coronary occlusion (60 minutes) followed by 42-day reperfusion. Heart function was assessed echocardiographically. Molecular signalling and proposed mechanisms (oxidative stress, collagen deposition and inflammation) were investigated in whole hearts and in subcellular fractions when appropriate. In post-infarction failing hearts, TNF and pSer229-RIP3 levels were comparably increased in both infarcted and non-infarcted areas. Its cytotoxic downstream molecule p-MLKL, indicating necroptosis execution, was detected in infarcted area. In non-infarcted area, despite increased pSer229-RIP3, p-MLKL was present in neither whole cells nor the cell membrane known to be associated with necroptosis execution. Likewise, increased membrane lipoperoxidation and NOX2 levels unlikely promoted pro-necroptotic environment in non-infarcted area. Collagen deposition and the inflammatory csp-1-IL-1 beta axis were active in both areas of failing hearts, while being more pronounced in infarcted tissue. Although apoptotic proteins were differently expressed in infarcted and non-infarcted tissue, apoptosis was found to play an insignificant role. p-MLKL-driven necroptosis and inflammation while inflammation only (without necroptotic cell death) seem to underlie fibrotic healing and progressive injury in infarcted and non-infarcted areas of failing hearts, respectively. Upregulation of pSer229-RIP3 in both HF areas suggests that this kinase, associated with both necroptosis and inflammation, is likely to play a dual role in HF progression.

Czech name

—

Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30201 - Cardiac and Cardiovascular systems

Project

<a href="/en/project/NV15-27735A" target="_blank" >NV15-27735A: Progression of chronic heart failure and cardiorenal syndrome in hypertensive rats after myocardial infarction: role of epoxyeicosatrienoic acids.</a><br>

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2019

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Journal of Cellular and Molecular Medicine

ISSN

1582-4934

e-ISSN

—

Volume of the periodical

23

Issue of the periodical within the volume

9

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

6429-6441

UT code for WoS article

000484153100001

EID of the result in the Scopus database

2-s2.0-85071494302