title: Oxidative stress and cardiomyocyte necrosis with elevated serum troponins: pathophysiologic mechanisms.
abstract: The progressive nature of heart failure is linked to multiple factors, including an ongoing loss of cardiomyocytes and necrosis. Necrotic cardiomyocytes leave behind several footprints: the spillage of their contents leading to elevations in serum troponins; and morphologic evidence of tissue repair with scarring. The pathophysiologic origins of cardiomyocyte necrosis relates to neurohormonal activation, including the adrenergic nervous system. Catecholamine-initiated excessive intracellular Ca accumulation and mitochondria Ca overloading in particular initiate a mitochondriocentric signal-transducer-effector pathway to necrosis and which includes the induction of oxidative stress and opening of their inner membrane permeability transition pore. Hypokalemia, ionized hypocalcemia and hypomagnesemia, where consequent elevations in parathyroid hormone further account for excessive intracellular Ca accumulation, hypozincemia and hyposelenemia each compromise metalloenzyme-based antioxidant defenses. The necrotic loss of cardiomyocytes and adverse structural remodeling of myocardium is related to the central role played by a mitochondriocentric pathway initiated by neurohormonal activation.
authors: Division of Cardiovascular Diseases, University of Tennessee Health Science Center, Memphis 38163, USA.
authors: Antwon D
authors: AD
authors: Robinson
authors: Kodangudi B
authors: KB
authors: Ramanathan
authors: Jesse E
authors: JE
authors: McGee
authors: Kevin P
authors: KP
authors: Newman
authors: Karl T
authors: KT
authors: Weber
mesh_terms: D000818:Animals; D005355:Fibrosis; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000378:metabolism / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D009336:Necrosis; D018384:Oxidative Stress / Q000502:physiology*; D014336:Troponin / Q000097:blood* / Q000378:metabolism / Q000502:physiology
chemical_list: D014336:Troponin