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- W2109686719 abstract "Loss of cardiac myocytes in heart failure is thought to occur largely through an apoptotic process. Here we show that heart failure can also be precipitated through myocyte necrosis associated with Ca2+ overload. Inducible transgenic mice with enhanced sarcolemmal L-type Ca2+ channel (LTCC) activity showed progressive myocyte necrosis that led to pump dysfunction and premature death, effects that were dramatically enhanced by acute stimulation of beta-adrenergic receptors. Enhanced Ca2+ influx-induced cellular necrosis and cardiomyopathy was prevented with either LTCC blockers or beta-adrenergic receptor antagonists, demonstrating a proximal relationship among beta-adrenergic receptor function, Ca2+ handling, and heart failure progression through necrotic cell loss. Mechanistically, loss of cyclophilin D, a regulator of the mitochondrial permeability transition pore that underpins necrosis, blocked Ca2+ influx-induced necrosis of myocytes, heart failure, and isoproterenol-induced premature death. In contrast, overexpression of the antiapoptotic factor Bcl-2 was ineffective in mitigating heart failure and death associated with excess Ca2+ influx and acute beta-adrenergic receptor stimulation. This paradigm of mitochondrial- and necrosis-dependent heart failure was also observed in other mouse models of disease, which supports the concept that heart failure is a pleiotropic disorder that involves not only apoptosis, but also necrotic loss of myocytes in association with dysregulated Ca2+ handling and beta-adrenergic receptor signaling." @default.
- W2109686719 created "2016-06-24" @default.
- W2109686719 creator A5000001455 @default.
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- W2109686719 date "2007-09-04" @default.
- W2109686719 modified "2023-09-22" @default.
- W2109686719 title "Ca2+- and mitochondrial-dependent cardiomyocyte necrosis as a primary mediator of heart failure" @default.
- W2109686719 cites W1591646293 @default.
- W2109686719 cites W1607777232 @default.
- W2109686719 cites W166385710 @default.
- W2109686719 cites W171374847 @default.
- W2109686719 cites W1892519879 @default.
- W2109686719 cites W1971034264 @default.
- W2109686719 cites W1980142871 @default.
- W2109686719 cites W1986866353 @default.
- W2109686719 cites W1988522933 @default.
- W2109686719 cites W1992467460 @default.
- W2109686719 cites W1993536160 @default.
- W2109686719 cites W1994103758 @default.
- W2109686719 cites W1994740184 @default.
- W2109686719 cites W1999215577 @default.
- W2109686719 cites W1999218550 @default.
- W2109686719 cites W2002439304 @default.
- W2109686719 cites W2002958873 @default.
- W2109686719 cites W2005654557 @default.
- W2109686719 cites W2019435811 @default.
- W2109686719 cites W2021984762 @default.
- W2109686719 cites W2023482296 @default.
- W2109686719 cites W2023650178 @default.
- W2109686719 cites W2023928179 @default.
- W2109686719 cites W2031832454 @default.
- W2109686719 cites W2032580133 @default.
- W2109686719 cites W2040337560 @default.
- W2109686719 cites W2042142184 @default.
- W2109686719 cites W2044860026 @default.
- W2109686719 cites W2046073283 @default.
- W2109686719 cites W2049365481 @default.
- W2109686719 cites W2051304606 @default.
- W2109686719 cites W2051673088 @default.
- W2109686719 cites W2054578176 @default.
- W2109686719 cites W2058945985 @default.
- W2109686719 cites W2063099262 @default.
- W2109686719 cites W2063654473 @default.
- W2109686719 cites W2063807479 @default.
- W2109686719 cites W2064657449 @default.
- W2109686719 cites W2064705407 @default.
- W2109686719 cites W2068671266 @default.
- W2109686719 cites W2070352761 @default.
- W2109686719 cites W2074137489 @default.
- W2109686719 cites W2074800090 @default.
- W2109686719 cites W2084443378 @default.
- W2109686719 cites W2088236700 @default.
- W2109686719 cites W2088629175 @default.
- W2109686719 cites W2090502913 @default.
- W2109686719 cites W2090544953 @default.
- W2109686719 cites W2093618064 @default.
- W2109686719 cites W2094765038 @default.
- W2109686719 cites W2108383919 @default.
- W2109686719 cites W2112798012 @default.
- W2109686719 cites W2114235073 @default.
- W2109686719 cites W2122726052 @default.
- W2109686719 cites W2122728009 @default.
- W2109686719 cites W2131912652 @default.
- W2109686719 cites W2132374854 @default.
- W2109686719 cites W2136546365 @default.
- W2109686719 cites W2137625135 @default.
- W2109686719 cites W2140313980 @default.
- W2109686719 cites W2140608810 @default.
- W2109686719 cites W2142377849 @default.
- W2109686719 cites W2143577214 @default.
- W2109686719 cites W2143827483 @default.
- W2109686719 cites W2149396086 @default.
- W2109686719 cites W2149495528 @default.
- W2109686719 cites W2151825667 @default.
- W2109686719 cites W2151912878 @default.
- W2109686719 cites W2154201149 @default.
- W2109686719 cites W2156979262 @default.
- W2109686719 cites W2158800467 @default.
- W2109686719 cites W2161568820 @default.
- W2109686719 cites W2164186142 @default.
- W2109686719 cites W2168847839 @default.
- W2109686719 cites W2171728648 @default.
- W2109686719 cites W2345912369 @default.
- W2109686719 cites W2792980560 @default.
- W2109686719 cites W4229759864 @default.
- W2109686719 cites W4235201972 @default.
- W2109686719 cites W4235557943 @default.
- W2109686719 cites W4240337538 @default.