Long Non-coding RNA PEBP1P2 Suppresses Proliferative VSMCs Phenotypic Switching and Proliferation in Atherosclerosis

被引：57

作者：

He, Xingqiang ^{[1
,3
]}

Lian, Zhexun ^{[1
]}

Yang, Yanyan ^{[4
]}

Wang, Zhibin ^{[5
]}

Fu, Xiuxiu ^{[5
]}

Liu, Yan ^{[2
]}

Li, Min ^{[2
]}

Tian, Jiawei ^{[6
]}

Yu, Tao ^{[2
,5
]}

Xin, Hui ^{[1
]}

机构：

[1] Qingdao Univ, Affiliated Hosp, Dept Cardiol, 16 Jiangsu Rd, Qingdao 266000, Shandong, Peoples R China

[2] Qingdao Univ, Affiliated Hosp, Inst Translat Med, Qingdao 266021, Shandong, Peoples R China

[3] Shaanxi Univ Chinese Med, Affiliated Hosp 2, Dept Cardiol, Xianyang 712000, Shaanxi, Peoples R China

[4] Qingdao Univ, Sch Basic Med, Dept Immunol, Qingdao 266071, Shandong, Peoples R China

[5] Qingdao Univ, Affiliated Hosp, Dept Cardiac Ultrasound, Qingdao 266000, Shandong, Peoples R China

[6] Qingdao Univ, Affiliated Hosp, Dept Emergency Internal Med, Qingdao 266000, Shandong, Peoples R China

来源：

MOLECULAR THERAPY-NUCLEIC ACIDS | 2020年 / 22卷

基金：

中国国家自然科学基金;

关键词：

SMOOTH-MUSCLE-CELLS; DEPENDENT KINASE 9; CARDIOVASCULAR-DISEASE; CDK9; INFLAMMATION; MECHANISMS; MIGRATION;

D O I：

10.1016/j.omtn.2020.08.013

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Long non-coding RNAs (lncRNAs) play a crucial role in the growth of vascular smooth muscle cells (VSMCs), the dysfunction of which is closely associated with the initiation and progression of cardiovascular diseases (CVDs). Abnormal phenotypic switching and proliferation of VSMCs constitute a significant event in the progression of atherosclerosis. The present study identified a novel lncRNA, PEBP1P2, which serves as a valuable regulator of VSMCs in phenotypic transformation and proliferation. The expression of PEBP1P2 was remarkably decreased in proliferating VSMCs and pathological arteries when using a balloon injury model of rats. Furthermore, we found that PEBP1P2 represses proliferation, migration, and dedifferentiation during phenotype switching in VSMCs induced by platelet-derived growth factor BB (PDGF-BB). Mechanistically, cyclin-dependent kinase 9 (CDK9) was confirmed to be the direct target of PEBP1P2, which was proven to mediate phenotypic switching and proliferation of VSMCs and was rescued by PEBP1P2. Then, we explored the clinical significance, as we observed the decreased expression of PEBP1P2 in the serum of coronary heart disease (CHD) patients and human advanced carotid atherosclerotic plaques. Finally, PEBP1P2 overexpression distinctly suppressed neointima formation and VSMC phenotypic switching in vivo. Taken together, PEBP1P2 inhibits proliferation and migration in VSMCs by directly binding to CDK9, implying that it maybe a promising therapeutic target for the treatment of proliferative vascular diseases.

引用

页码：84 / 98

页数：15

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