Dysferlin deficiency in mice leads to defective cardiomyocyte membrane repair and cardiomyopathy, which is exacerbated by mechanical stress or dystrophin deficiency.
Does dysferlin deficiency impair cardiomyocyte membrane repair and lead to cardiomyopathy under mechanical stress?
Dysferlin is essential for cardiomyocyte membrane repair, and its deficiency leads to cardiomyopathy that is exacerbated by mechanical stress or dystrophin loss.
Dilated cardiomyopathy is a life-threatening syndrome that can arise from a myriad of causes, but predisposition toward this malady is inherited in many cases. A number of inherited forms of dilated cardiomyopathy arise from mutations in genes that encode proteins involved in linking the cytoskeleton to the extracellular matrix, and disruption of this link renders the cell membrane more susceptible to injury. Membrane repair is an important cellular mechanism that animal cells have developed to survive membrane disruption. We have previously shown that dysferlin deficiency leads to defective membrane resealing in skeletal muscle and muscle necrosis; however, the function of dysferlin in the heart remains to be determined. Here, we demonstrate that dysferlin is also involved in cardiomyocyte membrane repair and that dysferlin deficiency leads to cardiomyopathy. In particular, stress exercise disturbs left ventricular function in dysferlin-null mice and increases Evans blue dye uptake in dysferlin-deficient cardiomyocytes. Furthermore, a combined deficiency of dystrophin and dysferlin leads to early onset cardiomyopathy. Our results suggest that dysferlin-mediated membrane repair is important for maintaining membrane integrity of cardiomyocytes, particularly under conditions of mechanical stress. Thus, our study establishes what we believe is a novel mechanism underlying the cardiomyopathy that results from a defective membrane repair in the absence of dysferlin.
Han et al. (Mon,) conducted a other in Cardiomyopathy. Dysferlin deficiency vs. Wild-type (WT) mice was evaluated on Cardiomyocyte membrane repair and left ventricular function. Dysferlin deficiency in mice leads to defective cardiomyocyte membrane repair and cardiomyopathy, which is exacerbated by mechanical stress or dystrophin deficiency.