Excess ischemic tachyarrhythmias trigger protection against myocardial infarction in hypertensive rats
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
34486670
DOI
10.1042/cs20210648
PII: 229720
Knihovny.cz E-resources
- Keywords
- C-reactive protein, heart, metabolomics, myocardial infarction, remote ischemic perconditioning, ventricular arrhythmias,
- MeSH
- Action Potentials MeSH
- C-Reactive Protein genetics metabolism MeSH
- Ventricular Fibrillation etiology metabolism physiopathology MeSH
- Hypertension complications metabolism physiopathology MeSH
- Tachycardia, Ventricular etiology metabolism physiopathology MeSH
- Blood Pressure MeSH
- Rats MeSH
- Humans MeSH
- Disease Models, Animal MeSH
- Myocardium metabolism pathology MeSH
- Rats, Inbred SHR MeSH
- Rats, Transgenic MeSH
- Myocardial Reperfusion Injury etiology metabolism physiopathology prevention & control MeSH
- Heart Rate MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Humans MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- C-Reactive Protein MeSH
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.
4th Department of Medicine 1st Faculty of Medicine Charles University Prague Czech Republic
Biomedical Centre Faculty of Medicine in Pilsen Charles University Prague Czech Republic
Department of Physiology Faculty of Science Charles University Prague Czech Republic
Institute of Anatomy 1st Faculty of Medicine Charles University Prague Czech Republic
References provided by Crossref.org
Sixty Years of Heart Research in the Institute of Physiology of the Czech Academy of Sciences
