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Protection mechanism of myocardial tissues of Wnt/β-catenin signaling inhibition by GAS5 in rats with coronary artery disease

Published on May. 31, 2025Total Views: 180 times Total Downloads: 23 times Download Mobile

Author: WANG Qunye 1 LI Chunhong 2 XU Lu 2

Affiliation: 1. Department of Internal Medicine, Harbin Jiarun Hospital, Harbin 161000, China 2. Department of Cardiology, The First Affiliated Hospital of Qiqihar Medical College, Qiqihar 161006, Heilongjiang Province, China

Keywords: Growth arrest-specific 5 Wnt/β-catenin signaling pathway Coronary heart disease Myocardial injury Myocardial enzymes Apoptosis

DOI: 10.12173/j.issn.2097-4922.202502044

Reference: WANG Qunye, LI Chunhong, XU Lu. Protection mechanism of myocardial tissues of Wnt/β-catenin signaling inhibition by GAS5 in rats with coronary artery disease[J]. Yaoxue QianYan Zazhi, 2025, 29(5): 739-746. DOI: 10.12173/j.issn.2097-4922.202502044.[Article in Chinese]

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Abstract

Objective  To study the mechanism of by which long-chain non-coding RNA growth arrest- specific transcript 5 (LncRNA GAS5) protects myocardial tissues in rats with coronary artery disease (CHD) by inhibiting the abnormal activation of Wnt/β-catenin signaling pathway.

Methods  According to different models, 60 clean-grade healthy SD rats were divided into the control group, the CHD group and the GAS5 overexpression group, with 20 rats in each group. The rats in the control group were transfected with empty vector plasmid, and the CHD model was constructed in CHD group and GAS5 overexpression group. On this basis, the CHD+GAS5 overexpression group was injected intravenously with pcDNA3.1-GAS5 once a day for 5 d. RT-qPCR was applied to detect the mRNA expression levels of GAS5, Wnt-1, β-catenin and c-Myc in the cardiac tissues of the three groups of rats. The expression levels of TC, TG, HDL-C and LDL-C were determined using modular DPP automatic biochemical analyzer ; the oxidation stress index and SOD levels in myocardial tissues were detected using the pyrogallol autoxidation method; the expression levels of cardiac myosin enzymes CK-MB, cTnI, MDA, and GAS5 in the serum of rats were detected by ELISA; Western blot (WB) was used to detect the protein expression levels of Bax, Bcl2, Wnt-1, β-catenin and c-Myc in rat myocardial tissues.

Results  Compared with rats in the control group, serum TC, TG, HDL-C, MDA, CK-MB, and cTnI levels were significantly higher in the CHD group (P<0.05), while GAS5 mRNA SOD and LDL-C levels were significantly lower (P<0.05). Compared with rats in the CHD group, serum TC, TG, HDL-C, MDA, CK-MB and cTnI levels were significantly lower in the GAS5 overexpression group (P<0.05), while GAS5 mRNA SOD and LDL-C levels were significantly higher (P<0.05). Compared with the control group, myocardial tissues of the CHD group showed a significant increase in Bax protein, and protein and mRNA expression of Wnt-1, β-catenin and c-Myc (P<0.05) all increased, while the Bcl-2 protein significantly decreased (P<0.05). Compared with rats in the CHD group, myocardial tissues in the GAS5 overexpression group showed a significant decrease in Bax protein expression, a decrease in protein and mRNA expression of Wnt-1, β-catenin, and c-Myc (P<0.05), and a significant increase in Bcl-2 protein (P<0.05).

Conclusion  Overexpression of GAS5 attenuated myocardial oxidative stress injury and inhibited cardiomyocyte apoptosis in CHD rats, and its mechanism may be to achieve the protective effect on myocardium by inhibiting the abnormal activation of Wnt/β-catenin signaling pathway in myocardial tissues.

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