Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats. Issue 17 (17th September 2021)

• Record Type: Journal Article
• Authors: Neckář, Jan; Alánová, Petra; Olejníčková, Veronika; Papoušek, František; Hejnová, Lucie; Šilhavý, Jan; Behuliak, Michal; Bencze, Michal; Hrdlička, Jaroslav; Vecka, Marek; Jarkovská, Dagmar; Švíglerová, Jitka; Mistrová, Eliška; Štengl, Milan; Novotný, Jiří; Ošťádal, Bohuslav; Pravenec, Michal; Kolář, František
• Is Part Of: Clinical science. Volume 135:Issue 17(2021)
• Page Start: 2143
• Page End: 2163
• Publication Date: 2021-09-17
• Subjects: C-reactive protein -- heart -- metabolomics -- myocardial infarction -- remote ischemic perconditioning -- ventricular arrhythmias; Medicine -- Periodicals; Biochemistry -- Periodicals; 616
• DOI: 10.1042/CS20210648
• Languages: English
• ISSNs: 0143-5221

Abstract

Abstract: 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.