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Br J Pharmacol. 2017 Jun;174(12):1555-1569. doi: 10.1111/bph.13704. Epub 2017 Feb 8.

Effect of hypercholesterolaemia on myocardial function, ischaemia-reperfusion injury and cardioprotection by preconditioning, postconditioning and remote conditioning.

Author information

1
Laboratory of Pharmacology, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
2
Second Department of Cardiology, Medical School, National and Kapodistrian University of Athens, Attikon University Hospital, Athens, Greece.
3
School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
4
Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
5
Pharmahungary Group, Szeged, Hungary.
6
Cardiovascular Research Group, Department of Biochemistry, University of Szeged, Szeged, Hungary.
7
Department of Physiology, Justus-Liebig-University, Giessen, Germany.

Abstract

Hypercholesterolaemia is considered to be a principle risk factor for cardiovascular disease, having direct negative effects on the myocardium itself, in addition to the development of atherosclerosis. Since hypercholesterolaemia affects the global cardiac gene expression profile, among many other factors, it results in increased myocardial oxidative stress, mitochondrial dysfunction and inflammation triggered apoptosis, all of which may account for myocardial dysfunction and increased susceptibility of the myocardium to infarction. In addition, numerous experimental and clinical studies have revealed that hyperlcholesterolaemia may interfere with the cardioprotective potential of conditioning mechanisms. Although not fully elucidated, the underlying mechanisms for the lost cardioprotection in hypercholesterolaemic animals have been reported to involve dysregulation of the endothelial NOS-cGMP, reperfusion injury salvage kinase, peroxynitrite-MMP2 signalling pathways, modulation of ATP-sensitive potassium channels and apoptotic pathways. In this review article, we summarize the current knowledge on the effect of hypercholesterolaemia on the non-ischaemic and ischaemic heart as well as on the cardioprotection induced by drugs or ischaemic preconditioning, postconditioning and remote conditioning. Future perspectives concerning the mechanisms and the design of preclinical and clinical trials are highlighted.

LINKED ARTICLES:

This article is part of a themed section on Redox Biology and Oxidative Stress in Health and Disease. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.12/issuetoc.

PMID:
28060997
PMCID:
PMC5446572
DOI:
10.1111/bph.13704
[Indexed for MEDLINE]
Free PMC Article

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