趋化因子CXCL12/趋化因子受体CXCR7轴与心血管疾病的相关性

Relevance of the chemokine CXCL12/CXCR7 axis in cardiovascular disease

摘要:

趋化因子CXCL12 （chemokine CXCL12，CXCL12）是一种能诱导细胞向高浓度方向定向运动的小分子多肽类物质，研究表明其能够通过调节造血干细胞、祖细胞的归巢、迁移及动员至外周环境，来保护组织在损伤刺激下的自我稳态。既往研究认为CXCL12的唯一受体是趋化因子受体4（C-X-C chemokine receptor 4，CXCR4），但研究表明其还存在另一个受体：趋化因子受体7（C-X-C chemokine receptor 7，CXCR7），它是一个非典型趋化因子受体家族，且不是通过激活G蛋白偶联受体而是通过与β抑制蛋白类相互作用，调节CXCL12的生物利用率以及上调或者下调CXCR4介导的活性及信号通路。本文主要讨论CXCR7在细胞增殖、血管生成、及细胞迁移方面的作用，以及其与心血管疾病之间的相关性。

Abstract:

Objective：Chemokine receptor CXCL12 is a small protein that mediates cell chemotaxis. Previous studies confirmed that chemokine receptor CXCL12 was a principal regulator of homing，migration and mobilization of haematopoietic stem cells and endothelial pro－genitor cells（EPCs） during steady-state homeostasis and injury. Once previously thought to interact exclusively with CXCR4，CXCL12 also binds to CXCR7（recently renamed ACK3R），which belongs to an atypical chemokine receptor family whose members fail to ac－tivate G proteins but interact with β-arrestins，control the CXCL12 bioavailability，enhance or dampen CXCR4- mediated signaling and activity.Here we discuss the role of CXCR7 in cell proliferation，angiogenesis，and metastasis，with a focus on cardiovascular dis－ease.