例如:"lncRNA", "apoptosis", "WRKY"

Dynamin-2 mediates heart failure by modulating Ca2+ -dependent cardiomyocyte apoptosis.

Int. J. Cardiol.2013 Oct 3;168(3):2109-19. Epub 2013 Feb 11
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摘要


BACKGROUND:Heart failure (HF) is approaching an epidemic proportion and has become one of the leading causes of death. It imposes a great burden on the healthcare system and society. Remodeling of cardiomyocyte membranes has a profound role in the pathogenesis of HF. However, whether dynamin (DNM), a membrane-remodeling GTPase, is associated with HF remains unclear. METHODS AND RESULTS:Here, we identified that DNM2 is necessary for the maintenance of cardiac function. Endogenous DNM2 protein levels were gradually decreased in parallel with the progression of HF in different experimental animal models. Decreased DNM2 level was also observed in the end-stage failing human heart. DNM2-deficient zebrafish exhibited signs of notable cardiac apoptosis and eventually developed severe HF. Mechanistic study showed that DNM2 downregulation caused cardiomyocyte sarcoplasmic reticulum Ca(2+) overload and subsequent mitochondria-dependent apoptosis. These events were preceded by enhanced membrane translocation of the L-type Ca(2+) channel due to DNM2 deficiency-mediated membrane trafficking dysfunction. Furthermore, prevention of cardiomyocyte Ca(2+)-mishandling largely ameliorated the DNM2 deficiency-associated cardiomyocyte apoptosis and HF. CONCLUSIONS:DNM2 mediates HF by modulating Ca(2+)-dependent apoptotic death of cardiomyocyte. The finding may shed light on the new strategy of HF treatment.

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