Department of Intensive Care Unit, The Affiliated Hospital of Qingdao University, Qingdao, China.
Department of Cardiology, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, People's Republic of China.
Mol Cell Biochem. 2020 Sep;472(1-2):241-251. doi: 10.1007/s11010-020-03802-x. Epub 2020 Jul 6.
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.
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.
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.
分泌型卷曲相关蛋白 2（sFRP2）已被报道参与心血管疾病。然而，其在压力超负荷引起的心肌肥厚中的作用仍不清楚。我们旨在研究 sFRP2 在体内和体外心肌肥厚中的作用。
在主动脉缩窄（AB）刺激心肌肥厚后，sFRP2 的表达在肥厚的心室中下调。通过尾静脉注射腺相关病毒 9（AAV9）在小鼠心肌中过表达 sFRP2。sFRP2 的过表达减轻了心肌细胞肥大和间质纤维化，表现为心肌细胞横截面积、心脏重量/体重比和左心室（LV）胶原比降低。此外，sFRP2 减少了压力超负荷诱导的心肌细胞凋亡。Western blot 显示 sFRP2 阻止了活性 β-连环蛋白的表达。Wnt/β-连环蛋白激动剂 LiCl（1mmol/kg）消除了 sFRP2 对心肌肥厚和凋亡的抑制作用，表现为横截面积和 LV 胶原比增加，以及超声心动图数据恶化。
我们的研究表明，衰竭小鼠心脏中观察到 sFRP2 水平降低。sFRP2 的过表达通过抑制 Wnt/β-连环蛋白通路减轻了肥大刺激诱导的心肌细胞肥大和间质纤维化。我们揭示了 sFRP2 可能是心脏重塑发展的有前途的治疗靶点。
