下调CD36促进肥厚型心肌病中内皮细胞的增殖

Down-regulation CD36 increased proliferation of endothelial cell in hypertrophic cardiomyopathy

目的探讨巨噬细胞分化抗原36(CD36)在肥厚型心肌病(HCM)中对内皮细胞增殖的影响及其潜在机制。方法通过实验检查CD36对HCM中内皮细胞增殖及其潜在机制的影响。通过分析cTnT^(R92Q)转基因小鼠心肌中CD36的表达来补充这项研究。此外,通过转染CD36基因或使用siRNA-CD36处理从cTnT^(R92Q)转基因小鼠心脏中分离的内皮细胞进行体外分析。结果在本研究中,我们观察到与野生型小鼠(WT)相比,cTnT^(R92Q)转基因小鼠心肌组织中CD36表达升高,微血管密度减少。此外,cTnT^(R92Q)转基因小鼠中内皮细胞的增殖减少。然而,将siRNA-CD36转染到内皮细胞中却产生了相反的结果。进一步的研究揭示了下调CD36增加了p-VEGFR2的表达,并增强了内皮细胞的增殖。EGFR特异性抑制剂AG1478逆转了这些效应。结论下调CD36增强了p-VEGFR2的表达,并促进了HCM中内皮细胞的增殖。这意味着降低CD36表达可能是治疗HCM中心肌缺血的一种有前途的治疗方法。

Objective To investigate the impact of cluster of differentiation 36(CD36)on endothelial cell proliferation and its underlying mechanisms in hypertrophic cardiomyopathy(HCM).Methods This investigation employed cTnT^(R92Q)transgenic mice as the experimental group and wild-type mice(WT)as control to assess myocardial microvessel density and CD36 expression in myocardial tissue across both groups.Utilizing myocardial microvascular endothelial cells(MVECs)as the substrate,the modulation of CD36 expression was undertaken to elucidate the influence of CD36 on endothelial cell proliferation in HCM.Results In this study,compared to wild-type(WT)mice elevated CD36 expression coupled with decreased microvessel density in the myocardial tissue of cTnT^(R92Q)transgenic mice was observed.Moreover,endothelial cell proliferation was reduced in the cTnT^(R92Q)transgenic mice.However,transfecting siRNA-CD36 into the endothelial cells resulted in opposite findings.Further investigations revealed that down-regulating CD36 increased p-VEGFR2 expression and enhanced endothelial cell proliferation.The EGFR specific inhibitor AG1478 reversed these effects.Conclusions The findings suggest that down-regulating CD36 enhances p-VEGFR2 expression and promotes endothelial cell proliferation in HCM.This implies that reducing CD36 expression could be a promising therapeutic approach for treating myocardial ischemia in HCM.