Key result
YAP knockdown reduces fibrosis and improves cardiac function in diabetic rats by decreasing CTGF and fibronectin.
Why the study?
YAP is related to cardiovascular disease pathology, but its role in cardiac injury of diabetic cardiomyopathy is still unclear.
Does YAP knockdown reduce myocardial fibrosis and improve cardiac function in a rat model of diabetic cardiomyopathy?
Does YAP knockdown reduce myocardial fibrosis and improve cardiac function in a rat model of diabetic cardiomyopathy?
YAP knockdown reduces myocardial fibrosis and improves cardiac function in a rat model of diabetic cardiomyopathy, identifying YAP as a potential therapeutic target.
Answers are grounded in this paper and cite their sources.
Does not change clinical practice in diabetic cardiomyopathy; leaves open YAP as a therapeutic target pending human studies.
INTRODUCTION: Recent studies have shown that YAP is closely related to the pathological process of cardiovascular diseases. But the role of YAP in cardiac injury of diabetic cardiomyopathy (DCM) is still unclear. METHODS: Diabetic cardiomyopathy rat model was established and divided into control group, DCM group, LV-SC-shRNA group and LV-YAP-shRNA group. LV-SC-shRNA group and LV-YAP-shRNA group were injected with lentivirus expressing SC-shRNA and YAP-shRNA via tail vein, respectively. Primary rat cardiac fibroblasts (CFs) were stimulated with high concentration of glucose and treated with recombinant lentivirus expressing either SC-shRNA or YAP-shRNA to observe the expression of CTGF and fibronectin, so as to observe the effect of inhibiting YAP on the pathogenesis of DCM. RESULTS: Compared with control group, high glucose markedly increased YAP mRNA and protein expression in DCM and CFs. Inhibition of YAP decreased myocardial fibrosis and improved cardiac function in the DCM model and decreased the expression of CTGF and fibronectin in CFs. The result suggested that YAP plays a key role in the pathological progression of DCM, and the underlying mechanisms may be associated with TEAD and CTGF. DISCUSSION: We found that the expression of YAP was increased both in vivo and in vitro, suggesting that YAP is closely related to DCM, and YAP knockdown can reduce myocardial fibrosis in rat model of DCM by reducing the expression of PAI-1, collagen I, collagen III, CTGF and profilin, as well as the expression of CTGF and fibronectin in CFs. This study revealed that YAP plays an important role in the pathological process of diabetic cardiomyopathy, and down-regulation of YAP expression may provide a new therapeutic target for DCM.
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Hu et al. (2021) studied Diabetic cardiomyopathy. YAP-shRNA vs. SC-shRNA and untreated DCM control was evaluated on Myocardial fibrosis, cardiac function, and expression of CTGF and fibronectin. YAP knockdown reduced myocardial fibrosis and improved cardiac function in a rat model of diabetic cardiomyopathy by decreasing the expression of CTGF and fibronectin.
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