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Excess ischemic tachyarrhythmias trigger protection infarction in rats

SYSNO ASEP	0546478
Document Type	J - Journal Article
R&D Document Type	Journal Article
Subsidiary J	Článek ve WOS
Title	Excess ischemic tachyarrhythmias trigger protection infarction in rats
Author(s)	Neckář, Jan (FGU-C)_{RID, ORCID} Alánová, Petra (FGU-C)_{RID, ORCID} Olejníčková, Veronika (FGU-C)_{RID, ORCID, SAI} Papoušek, František (FGU-C) Hejnová, L. (CZ) Šilhavý, Jan (FGU-C)_{RID, ORCID} Behuliak, Michal (FGU-C)_{RID, ORCID} Bencze, Michal (FGU-C)_{RID, ORCID, SAI} Hrdlička, Jaroslav (FGU-C)_{ORCID, RID} Vecka, M. (CZ) Jarkovská, D. (CZ) Švíglerová, J. (CZ) Mistrová, E. (CZ) Štengl, M. (CZ) Novotný, J. (CZ) Ošťádal, Bohuslav (FGU-C)_{RID, ORCID} Pravenec, Michal (FGU-C)_{RID, ORCID} Kolář, František (FGU-C)_{RID, ORCID, SAI}
Source Title	Clinical science. - : Portland Press - ISSN 0143-5221 Roč. 135, č. 17 (2021), s. 2143-2163
Number of pages	21 s.
Language	eng - English
Country	GB - United Kingdom
Keywords	C-reactive protein ; heart ; metabolomics ; myocardial infarction ; remote ischemic perconditioning ; ventricular arrhythmias
Subject RIV	ED - Physiology
OECD category	Physiology (including cytology)
R&D Projects	GA18-03207S GA ČR - Czech Science Foundation (CSF)
Method of publishing	Limited access
Institutional support	FGU-C - RVO:67985823
UT WOS	000702536100001
EID SCOPUS	85116954913
DOI	10.1042/CS20210648
Annotation	Increased level of C-reactive protein (CRP) is a risk factor for cardiovascular diseases, including myocardial infarction and hypertension. Here, we analyzed the effects of CRP overexpression on cardiac susceptibility to ischemia/reperfusion (I/R) injury in adult spontaneously hypertensive rats (SHR) expressing human CRP transgene (SHR-CRP). Using an in vivo model of coronary artery occlusion, we found that transgenic expression of CRP predisposed SHR-CRP to repeated and prolonged ventricular tachyarrhythmias. Excessive ischemic arrhythmias in SHR-CRP led to a significant reduction in infarct size (IS) compared with SHR. The proarrhythmic phenotype in SHR-CRP was associated with altered heart and plasma eicosanoids, myocardial composition of fatty acids (FAs) in phospholipids, and autonomic nervous system imbalance before ischemia. To explain unexpected IS-limiting effect in SHR-CRP, we performed metabolomic analysis of plasma before and after ischemia. We also determined cardiac ischemic tolerance in hearts subjected to remote ischemic perconditioning (RIPer) and in hearts ex vivo. Acute ischemia in SHR-CRP markedly increased plasma levels of multiple potent cardioprotective molecules that could reduce IS at reperfusion. RIPer provided IS-limiting effect in SHR that was comparable with myocardial infarction observed in naïve SHR-CRP. In hearts ex vivo, IS did not differ between the strains, suggesting that extra-cardiac factors play a crucial role in protection. Our study shows that transgenic expression of human CRP predisposes SHR-CRP to excess ischemic ventricular tachyarrhythmias associated with a drop of pump function that triggers myocardial salvage against lethal I/R injury likely mediated by protective substances released to blood from hypoxic organs and tissue at reperfusion.
Workplace	Institute of Physiology
Contact	Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400
Year of Publishing	2022
Electronic address	https://doi.org/10.1042/CS20210648

Number of the records: 1