Authors

Ziyi Hu1, #, Jing Ye2, #, Wenwen Wu3, Ying Yi2, Lisha Chen2, Renliang Li2, Junyu Lai4, *

Departments

1Department of Emergency, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China - 2Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, PR China - 3Department of Nephrology, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China - 4Department of Cardiovascular Medicine, Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Nanchang 330006, PR China

Abstract

Objective: To investigate the effect of homocysteine (Hcy) induced heart failure mediated by microRNA-21 / homologous phosphatase tensin (miR-21/PTEN) and miR-21/programmed death factor-4 (miR-21/PDCD4) signaling pathways.

Methods: Sixty clean, healthy male Wistar rats were randomly selected and randomly divided into a study group and a control group with 30 rats each. The rats in the control group were fed a standard diet, and the rats in the study group were fed with 3% methionine. They were fed for 12 weeks. The cardiac function (IVS, LVES, LVED, and EF) was measured by color Doppler ultrasound. Serum Hcy and brain natriuretic peptide (BNP) levels were measured using enzyme-linked immunosorbent assay (ELISA). The cardiac mass index was calculated. The left ventricular tissue of rats was taken, and the pathological changes of the myocardium were observed by HE staining. TUNEL staining was used to observe the apoptosis of myocardial cells in the two groups, and the apoptosis index was calculated. The expression levels of Mir-21, PTEN, and PDCD4 were detected by real-time fluorescence quantitative PCR. The expression levels of PTEN and PDCD4 in the myocardium of the two groups were measured by Western blot.

Results: Compared with the control group, the levels of IVS, LVESD, and LVEDD in the study group were significantly decreased, and the EF level was significantly increased (P<0.01). Compared to the control group, the serum Hcy and BNP levels in the study group were significantly increased (P<0.01), and the heart weight index of the study group was significantly increased (P<0.01). In the control group, the myocardial cells were arranged regularly, the size was uniform, and the myocardial gap was small; in the study group, the arrangement of myocardial cells was disordered, the size was uneven, and the myocardial gap was significantly increased. Compared with the control group, the apoptosis index, miR-21, PTEN, and PDCD4 expression levels in the study group were significantly increased (P<0.01).

Conclusion: Feeding rats with 3% methionine could significantly increase the levels of Hcy and BNP in serum and promote cardiomyocyte apoptosis. MiR-21 / PTEN and miR-21 / PDCD4 signaling pathways may play an important role in Hcy induced heart failure.

Keywords

MiR-21/PTEN, miR-21/PDCD4 signaling pathway, homocysteine, heart failure.

DOI:

10.19193/0393-6384_2022_4_344