Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11110%2F21%3A10433067" target="_blank" >RIV/00216208:11110/21:10433067 - isvavai.cz</a>

Alternative codes found

RIV/00216208:11140/21:10433067 RIV/00216208:11310/21:10433067

Result on the web

<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gPHoSUKz6l" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=gPHoSUKz6l</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1042/CS20210648" target="_blank" >10.1042/CS20210648</a>

Result language

angličtina

Original language name

Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats

Original language description

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 naive 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.

Czech name

—

Czech description

—

Type

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

CEP classification

—

OECD FORD branch

30105 - Physiology (including cytology)

Project

<a href="/en/project/GA18-03207S" target="_blank" >GA18-03207S: Cardiac ischemic tolerance of spontaneously hypertensive rats expressing human C-reactive protein.</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2021

Confidentiality

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

Name of the periodical

Clinical Science

ISSN

0143-5221

e-ISSN

—

Volume of the periodical

135

Issue of the periodical within the volume

17

Country of publishing house

GB - UNITED KINGDOM

Number of pages

21

Pages from-to

2143-2163

UT code for WoS article

000702536100001

EID of the result in the Scopus database

2-s2.0-85116954913