Regulation and therapeutic strategies of 4-hydroxy-2-nonenal metabolism in heart disease.
4-Hydroxy-2-nonenal (4-HNE), a reactive aldehyde, is generated from polyunsaturated fatty acids (PUFAs) in biological membranes. Reactive oxygen species (ROS) generated during oxidative stress react with PUFAs to form aldehydes like 4-HNE, which inactivates proteins and DNA by forming hybrid covalent chemical addition compounds called adducts. The ensuing chain reaction results in cellular dysfunction and tissue damage. It includes a wide spectrum of events ranging from electron transport chain dysfunction to apoptosis. In addition, 4-HNE directly depresses contractile function, enhances ROS formation, modulates cell signaling pathways, and can contribute to many cardiovascular diseases, including atherosclerosis, myocardial ischemia-reperfusion injury, heart failure, and cardiomyopathy. Therefore, targeting 4-HNE could help reverse these pathologies. This review will focus on 4-HNE generation, the role of 4-HNE in cardiovascular diseases, cellular targets (especially mitochondria), processes and mechanisms for 4-HNE-induced toxicity, regulation of 4-HNE metabolism, and finally strategies for developing potential therapies for cardiovascular disease by attenuating 4-HNEinduced toxicity.
Division of Hypertension and Vascular Research, Department of Internal Medicine, Henry Ford Health System , Detroit, MI , USA.
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Mali
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Palaniyandi
D000447:Aldehydes / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D006331:Heart Diseases / Q000378:metabolism* / Q000628:therapy; D006801:Humans; D018384:Oxidative Stress / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction
D000447:Aldehydes; D017382:Reactive Oxygen Species; C027576:4-hydroxy-2-nonenal