Mitochondrial dysfunction and oxidative damage to sarcomeric proteins.
Hypertension is an important risk factor for the development of heart failure. Increased production of reactive oxygen species (ROS) contributes to cardiac dysfunction by activating numerous pro-hypertrophic signaling cascades and damaging the mitochondria, thus setting off a vicious cycle of ROS generation. The way in which oxidative stress leads to exacerbation of systolic and diastolic dysfunction is still unclear, however. In skeletal muscle and ischemic myocardium, increased ROS production causes preferential oxidation of myofibrillar proteins and provides a mechanistic link between oxidative damage and impaired contractility through disruption of actin-myosin interactions, enzymatic functions, calcium sensitivity, and efficiency of cross-bridge cycling. In this review, we summarize recent findings in the fields of heart failure and sarcomere biology and speculate that oxidative damage to myofibrils may contribute to the development of heart failure.
Bayeva
Marina
M
Feinberg Cardiovascular Research Institute, Northwestern University, Feinberg School of Medicine, 303 East Chicago Avenue, Tarry 14-733, Chicago, IL 60611, USA. mabayeva@northwestern.edu
Ardehali
Hossein
H
D000818:Animals; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008929:Mitochondria, Heart / Q000502:physiology / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction; D017202:Myocardial Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure
D009124:Muscle Proteins; D017382:Reactive Oxygen Species