Yes-Associated Protein is Involved in Myocardial Fibrosis in Rats with Diabetic Cardiomyopathy

Maomao Hu; Han Wang; Shengnan Li; Feng Yan; Changning Fu; Lei Li; Yalin Yu; Jie Xiong; Bo Dong

doi:10.2147/DMSO.S302466

Yes-Associated Protein is Involved in Myocardial Fibrosis in Rats with Diabetic Cardiomyopathy

Diabetes Metab Syndr Obes. 2021 May 13:14:2133-2143. doi: 10.2147/DMSO.S302466. eCollection 2021.

Authors

Maomao Hu^#^{1

2}, Han Wang^#^{1

2

3}, Shengnan Li^#^{1

2}, Feng Yan², Changning Fu^{1

2}, Lei Li^{1

2}, Yalin Yu^{1

2

4}, Jie Xiong^{1

2}, Bo Dong^{1

2

4}

Affiliations

¹ Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, 250012, People's Republic of China.
² Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, People's Republic of China.
³ Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People's Republic of China.
⁴ Department of Cardiology, Shandong Traditional Chinese Medicine University, Jinan, People's Republic of China.

^# Contributed equally.

Abstract

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.

Keywords: diabetic cardiomyopathy; myocardial fibrosis; yes-associated protein.

Grants and funding

This study was supported by National Natural Science Foundation of China (No. 81870283, 81570729, 82070382) and Program of Taishan Scholars Programme (No. ts 20190979).