Abstract
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetes-associated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. To determine whether USMG5 is related to the development of heart failure, we performed clinical and experimental studies. Microarray analysis showed that the expression levels of USMG5 were positively correlated with those of natriuretic peptide precursor A in the human failed myocardium. When endogenous z-usmg5 in zebrafish was disrupted using morpholino (MO) oligonucleotides, the pericardial sac and atrial areas were larger and ventricular fractional shortening was reduced compared to in the control MO group. The expression levels of natriuretic peptides were upregulated in the z-usmg5 MO group compared to in controls. Further, microarray analysis revealed that genes in the calcium signalling pathway were downregulated in the z-usmg5 MO group. These results demonstrate that DAPIT plays a crucial role in the development of heart failure associated with DCM and thus may be a therapeutic target for heart failure.
Highlights
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium
Whether diabetesassociated protein in insulin-sensitive tissue (DAPIT) contributes to ATP production and maintaining ATP concentrations in cardiomyocytes is unclear, several studies have revealed the functions of this protein
Ohsakaya et al showed that mitochondrial ATP production was significantly reduced in DAPIT-depleted HeLa cells[11], indicating that DAPIT plays a critical role in ATP production by mitochondrial ATP synthase
Summary
The pathogenesis of heart failure associated with dilated cardiomyopathy (DCM) may result in part from adenosine triphosphate (ATP) dysregulation in the myocardium. Under these conditions, diabetesassociated protein in insulin-sensitive tissue (DAPIT), which is encoded by the upregulated during skeletal muscle growth 5 (USMG5) gene, plays a crucial role in energy production by mitochondrial ATP synthase. Microarray analysis revealed that genes in the calcium signalling pathway were downregulated in the z-usmg[5] MO group These results demonstrate that DAPIT plays a crucial role in the development of heart failure associated with DCM and may be a therapeutic target for heart failure. We hypothesized that DAPIT, a component of ATP synthase, plays a crucial role in the pathogenesis of heart failure associated with DCM
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