干旱区生态环境知识资源中心(Arid): C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway

Arid

DOI	10.1093/cvr/cvad133
	C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway
	Liu, Aiting; Chen, Zhenwei; Li, Xiaoxue; Xie, Chen; Chen, Yanlian; Su, Xiaoyan; Chen, Ying; Zhang, Mengbi; Chen, Jie; Yang, Tiecheng; Shen, Jiangang; Huang, Hui
通讯作者	Huang, H
来源期刊	CARDIOVASCULAR RESEARCH
ISSN	0008-6363
EISSN	1755-3245
出版年	2023
卷号	119 期号:15 页码:2563-2578
英文摘要	Aims Vascular calcification (VC) predicts the morbidity and mortality in cardiovascular diseases. Vascular smooth muscle cells (VSMCs) osteogenic transdifferentiation is the crucial pathological basis for VC. To date, the molecular pathogenesis is still largely unclear. Notably, C5a-C5aR1 contributes to the development of cardiovascular diseases, and its closely related to physiological bone mineralization which is similar to VSMCs osteogenic transdifferentiation. However, the role and underlying mechanisms of C5a-C5aR1 in VC remain unexplored. Methods and results A cross-sectional clinical study was utilized to examine the association between C5a and VC. Chronic kidney diseases mice and calcifying VSMCs models were established to investigate the effect of C5a-C5aR1 in VC, evaluated by changes in calcium deposition and osteogenic markers. The cross-sectional study identified that high level of C5a was associated with increased risk of VC. C5a dose-responsively accelerated VSMCs osteogenic transdifferentiation accompanying with increased the expression of C5aR1. Meanwhile, the antagonists of C5aR1, PMX 53, reduced calcium deposition, and osteogenic transdifferentiation both in vivo and in vitro. Mechanistically, C5a-C5aR1 induced endoplasmic reticulum (ER) stress and then activated PERK-eIF2 alpha-ATF4 pathway to accelerated VSMCs osteogenic transdifferentiation. In addition, cAMP-response element-binding protein 3-like 1 (CREB3L1) was a key downstream mediator of PERK-eIF2a-ATF4 pathway which accelerated VSMCs osteogenic transdifferentiation by promoting the expression of COL1a1. Conclusions High level of C5a was associated with increased risk of VC, and it accelerated VC by activating the receptor C5aR1. PERK-eIF2aATF4-CREB3L1 pathway of ER stress was activated by C5a-C5aR1, hence promoting VSMCs osteogenic transdifferentiation. Targeting C5 or C5aR1 may be an appealing therapeutic target for VC.
类型	Article
语种	英语
收录类别	SCI-E
WOS记录号	WOS:001187618900001
WOS关键词	TRANSCRIPTION FACTOR 4 ; SMOOTH-MUSCLE-CELLS ; CREB/ATF-FAMILY ; COMPLEMENT C3A ; C5A RECEPTORS ; CALCIUM ; OASIS ; EXPRESSION ; ATHEROSCLEROSIS ; INHIBITION
WOS类目	Cardiac & Cardiovascular Systems
WOS研究方向	Cardiovascular System & Cardiology
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/395642
推荐引用方式 GB/T 7714	Liu, Aiting,Chen, Zhenwei,Li, Xiaoxue,et al. C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway[J],2023,119(15):2563-2578.
APA	Liu, Aiting.,Chen, Zhenwei.,Li, Xiaoxue.,Xie, Chen.,Chen, Yanlian.,...&Huang, Hui.(2023).C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway.CARDIOVASCULAR RESEARCH,119(15),2563-2578.
MLA	Liu, Aiting,et al."C5a-C5aR1 induces endoplasmic reticulum stress to accelerate vascular calcification via PERK-eIF2α-ATF4-CREB3L1 pathway".CARDIOVASCULAR RESEARCH 119.15(2023):2563-2578.