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.

译文

背景与目的:据报道,卷曲的相关蛋白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。
方法和结果:在主动脉束带(AB)刺激的心肌肥大之后,sFRP2的表达在肥厚性心室中被下调。通过尾静脉注射腺相关病毒9(AAV9)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。另外,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,这一点由横截面积和LV胶原比例的增加以及超声心动图数据的恶化所证明。
结论:我们的研究表明在衰竭的小鼠心脏中观察到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。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录