Colchicine Prevents Cardiac Rupture in Mice with Myocardial Infarction by Inhibiting P53-Dependent Apoptosis

被引:0
|
作者
Shen, Liang [1 ]
Huang, Shaodai [1 ]
Fan, Hongyan [1 ]
Zhai, Changlin [1 ]
机构
[1] Jiaxing Univ, Affiliated Hosp, Dept Cardiol, 1882 Zhonghuan South Rd, Jiaxing 314000, Zhejiang, Peoples R China
关键词
Cardiomyocytes; Fibroblasts; Infarct size; Border zone; HEART-FAILURE;
D O I
10.1536/ihj.23-448
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Cardiac rupture is a fatal complication following myocardial infarction (MI) and there are currently no effective pharmacological strategies for preventing this condition. In this study, we investigated the effect of colchicine on post-infarct cardiac rupture in mice and its underlying mechanisms. We induced MI in mice by permanently ligating the left anterior descending artery. Oral colchicine or vehicle was administered at a dose of 0.1 mg/kg/day from day 1 to day 7 after MI. Cultured neonatal cardiomyocytes and fibroblasts were exposed to normoxia or anoxia and treated with colchicine. Colchicine significantly improved the survival rate (colchicine, n = 46: 82.6% versus vehicle, n = 42: 61.9%, P < 0.05) at 1 week after MI. Histological analysis revealed colchicine significantly reduced the infarct size and the number of macrophages around the infarct area. Colchicine decreased apoptosis in the myocardium of the border zone and cultured cardiomyocytes and fibroblasts as assessed by TUNEL assay. Colchicine also attenuated the activation of p53 and decreased the expression of cleaved-caspase 3 and bax, as assessed by Colchicine prevents cardiac rupture via inhibition of apoptosis, which is attributable to the downregulation of p53 activity. Our findings suggest that colchicine may be a prospective preventive medicine for cardiac rupture, however, large clinical trials are required.
引用
收藏
页码:905 / 912
页数:8
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