Mitochondria as a source and target of lipid peroxidation products in healthy and diseased heart

Summary1. The heart is a highly oxidative organ in which cardiomyocyte turnover is virtually absent, making it particularly vulnerable to accumulation of lipid peroxidation products (LPP) formed as a result of oxidative damage.2. Reactive oxygen and nitrogen species are the most common electrophiles formed during lipid peroxidation and lead to the formation of both stable and unstable LPP. Of the LPP formed, highly reactive aldehydes are a well‐recognized causative factor in ageing and age‐associated diseases, including cardiovascular disease and diabetes.3. Recent studies have identified that the mitochondria are both a primary source and target of LPP, with specific emphasis on aldehydes in cardiomyocytes and how these affect the electron transport system and Ca 2+ balance.4. Numerous studies have found that there are functional consequences in the heart following exposure to specific aldehydes (acrolein, trans ‐2‐hexanal, 4‐hydroxynonenal and acetaldehyde). Because these LPP are known to form in heart failure, cardiac ischaemia–reperfusion injury and diabetes, they may have an underappreciated role in the pathophysiology of these disease processes.5. Lipid peroxidation products are involved in the transcriptional regulation of endogenous anti‐oxidant systems. Recent evidence demonstrates that transient increases in LPP may be beneficial in cardioprotection by contributing to mitohormesis (i.e. induction of anti‐oxidant systems) in cardiomyocytes. Thus, exploitation of the cardioprotective actions of the LPP may represent a novel therapeutic strategy for future treatment of heart disease.