Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
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Index Copernicus  – 161.11; MEiN – 140 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2020, vol. 29, nr 7, July, p. 803–812

doi: 10.17219/acem/121926

Publication type: original article

Language: English

License: Creative Commons Attribution 3.0 Unported (CC BY 3.0)

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Effects of miR-124-3p regulation of the p38MAPK signaling pathway via MEKK3 on apoptosis and proliferation of macrophages in mice with coronary atherosclerosis

Chuannan Zhai1,2,A,B,C,D,E, Hongliang Cong1,2,E,F, Kai Hou1,2,A,B,C, Yuecheng Hu2,A,B, Jingxia Zhang2,A,B, Yingyi Zhang2,A,B, Ying Zhang2,A,B, Hong Zhang2,A,B

1 School of Medicine, Nankai University, Tianjin, China

2 Department of Cardiology, Tianjin Chest Hospital, China

Abstract

Background. Atherosclerosis (AS) is the main cause of myocardial infarction and stroke. Macrophage apoptosis in the early stages can attenuate lesions, while in the late stage it is associated with AS plaque rupture.
Objectives. To explore the effects of miR-124-3p regulation of the p38MAPK signaling pathway via the MEKK3 gene on the apoptosis and proliferation of macrophages in mice with coronary AS.
Material and Methods. Fifty male apolipoprotein E (ApoE) −/− mice were equally assigned to a normal group and a coronary AS group. In the AS group, the mice were given a high-fat diet to establish a coronary AS model. The macrophages of the mice were isolated for culture and divided into 7 groups: normal, negative control (NC), control, miR-124-3p mimic, miR-124-3p inhibitor, si-MEKK3, and miR-124-3p inhibitor+si-MEKK3.
Results. Compared with the normal group, the AS group had lower expression levels of miR-124-3p and higher expression levels of MEKK3 and p-p38MAPK in the coronary artery tissue and peritoneal macrophages (all p < 0.050). We found that miR-124-3p could negatively regulate MEKK3 expression. Compared with the control group, the miR-124-3p mimic group and si-MEKK3 group had greater cell apoptosis rates and Bax levels, weaker cell proliferation and invasion abilities, slower cell cycle progression, and lower PCNA and Bcl-2 levels (all p < 0.050). This trend was also displayed in the miR-124-3p inhibitor+si-MEKK3 group when compared with the miR-124-3p inhibitor group, and in the si-MEKK3 group when compared with the miR-124-3p inhibitor+si-MEKK3 group (all p < 0.050).
Conclusion. miR-124-3p overexpression can downregulate MEKK3 expression and inhibit the expression of the p38MAPK signaling pathway, thereby inhibiting macrophage proliferation and promoting macrophage apoptosis in mice with coronary AS.

Key words

MiR-124-3p, macrophage, coronary atherosclerosis

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