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Secreted frizzled-related protein 2 prevents pressure-overload-induced cardiac hypertrophy by targeting the Wnt/β-catenin pathway.
Molecular and Cellular Biochemistry ( IF 4.3 ) Pub Date : 2020-07-06 , DOI: 10.1007/s11010-020-03802-x
Wen-Ying Wei 1 , Qing Zhao 2 , Wen-Zhong Zhang 2 , Mao-Jing Wang 2 , Yan Li 2 , Shi-Zhong Wang 3 , Ning Zhang 2
Affiliation  

Background and aim

Secreted frizzled-related protein 2 (sFRP2) has been reported to be involved in cardiovascular diseases. However, its role in cardiac hypertrophy induced by pressure overload is still elusive. We aimed to examine the role of sFRP2 in the development of cardiac hypertrophy in vivo and in vitro.

Methods and results

Following cardiac hypertrophy stimulated by aortic banding (AB), the expression of sFRP2 was downregulated in the hypertrophic ventricle. Adeno-associated virus 9 (AAV9) was injected through the tail vein to overexpress sFRP2 in the mouse myocardium. Overexpression of sFRP2 alleviated cardiomyocyte hypertrophy and interstitial fibrosis, as identified by the reduced cardiomyocyte cross-sectional area, heart weight/body weight ratio, and left ventricular (LV) collagen ratio. Additionally, sFRP2 decreased cardiomyocyte apoptosis induced by pressure overload. Western blot showed that sFRP2 prevented the expression of active β-catenin. The Wnt/β-catenin agonist LiCl (1 mmol/kg) abolished the inhibitory effects of sFRP2 on cardiac hypertrophy and apoptosis, as evidenced by the increased cross-sectional area and LV collagen ratio and the deterioration of echocardiographic data.

Conclusion

Our study indicated that decreased sFRP2 levels were observed in failing mouse hearts. Overexpression of sFRP2 attenuated myocyte hypertrophy and interstitial fibrosis induced by hypertrophic stimuli by inhibiting the Wnt/β-catenin pathway. We revealed that sFRP2 may be a promising therapeutic target for the development of cardiac remodeling.



中文翻译:

分泌的卷曲相关蛋白2通过靶向Wnt /β-catenin途径来防止压力超负荷引起的心肌肥大。

背景和目标

据报道,分泌的卷曲相关蛋白2(sFRP2)与心血管疾病有关。然而,它在由压力超负荷引起的心脏肥大中的作用仍然难以捉摸。我们旨在研究sFRP2在体内和体外心脏肥大发展中的作用。

方法与结果

在由主动脉束带(AB)刺激的心肌肥大之后,sFRP2的表达在肥厚型心室中被下调。腺相关病毒9(AAV9)通过尾静脉注射以在小鼠心肌中过表达sFRP2。sFRP2的过表达减轻了心肌肥大和间质纤维化,这通过减少的心肌细胞横截面积,心脏重量/体重比和左心室(LV)胶原蛋白比来确定。此外,sFRP2减少了压力超负荷引起的心肌细胞凋亡。Western印迹表明,sFRP2阻止了活性β-catenin的表达。Wnt /β-catenin激动剂LiCl(1 mmol / kg)取消了sFRP2对心脏肥大和细胞凋亡的抑制作用,

结论

我们的研究表明,在衰竭的小鼠心脏中观察到了sFRP2水平降低。sFRP2的过表达通过抑制Wnt /β-catenin途径减弱了肥厚性刺激诱导的心肌肥大和间质纤维化。我们发现,sFRP2可能是心脏重塑发展的有希望的治疗靶标。

更新日期:2020-08-17
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