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Updated: Mar 9, 2026
A Murine Closed-chest Model of Myocardial Ischemia and Reperfusion
Published on: July 17, 2012
Effect of hypercholesterolaemia on myocardial function, ischaemia-reperfusion injury and cardioprotection by
Ioanna Andreadou1, Efstathios K Iliodromitis2, Antigone Lazou3
1Laboratory of Pharmacology, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Athens, Greece.
Insights
High cholesterol (hypercholesterolaemia) damages the heart and impairs its protective mechanisms. This review explores how high cholesterol affects heart function and reduces cardioprotection, highlighting future research directions.
Area of Science:
- Cardiovascular Biology
- Redox Biology
- Molecular Medicine
Background:
- Hypercholesterolaemia is a major risk factor for cardiovascular disease, impacting myocardial function and atherosclerosis.
- It alters cardiac gene expression, leading to oxidative stress, mitochondrial dysfunction, and apoptosis, increasing infarction susceptibility.
- Hypercholesterolaemia can significantly diminish the heart's natural protective responses to injury.
Purpose of the Study:
- To review the effects of hypercholesterolaemia on the non-ischaemic and ischaemic heart.
- To examine how hypercholesterolaemia influences drug-induced and conditioning-based cardioprotection.
- To highlight future research avenues for understanding and managing these effects.
Main Methods:
- Literature review of experimental and clinical studies.
- Analysis of mechanisms underlying impaired cardioprotection in hypercholesterolaemia.
- Synthesis of current knowledge on hypercholesterolaemia's impact on cardiac health and protection.
Main Results:
- Hypercholesterolaemia induces myocardial oxidative stress, mitochondrial dysfunction, and inflammation-triggered apoptosis.
- Cardioprotective conditioning mechanisms are often compromised in hypercholesterolaemic states.
- Dysregulated signalling pathways (e.g., eNOS-cGMP, RISK,ynitrite-MMP2) and ion channels are implicated in lost cardioprotection.
Conclusions:
- Hypercholesterolaemia detrimentally affects myocardial function and susceptibility to infarction.
- Understanding the mechanisms of impaired cardioprotection is crucial for therapeutic development.
- Further preclinical and clinical studies are needed to address these challenges.
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.
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