Guan Xiuju, Liu Yue, An Yajuan, Wang Xinshuang, Wei Liping, Qi Xin
School of Graduate Studies, Tianjin University of Traditional Chinese Medicine, Tianjin, People's Republic of China.
Department of Cardiology, Tianjin Union Medical Center, Tianjin, People's Republic of China.
Diabetes Metab Syndr Obes. 2024 Aug 26;17:3151-3161. doi: 10.2147/DMSO.S465755. eCollection 2024.
Atherosclerosis (AS) is a chronic progressive inflammatory disease of the vascular wall and the primary pathological basis of cardiovascular and cerebrovascular disease. Focal adhesion kinase (FAK) and proline-rich tyrosine kinase 2 (Pyk2), two highly homologous members of the FAK family kinases, play critical roles in integrin signaling. They also serve as scaffolding proteins that contribute to the assembly of cellular signaling complexes that regulate cell survival, cell cycle progression, and cell motility. Research indicates that the FAK family kinases is involved in the gene regulation of vascular cells and that aberrant expression of this family is associated with pathological changes in vascular disease. These findings establish the FAK family kinases as a critical signaling mediator in atherosclerotic lesions and inhibition of its activity has the potential to attenuate the pathological progression of AS. This review highlights the indispensable role of the FAK family kinases in abnormal vascular smooth muscle cell proliferation, endothelial cell dysfunction, inflammation, and lipid metabolism associated with AS. We also summarize therapeutic targets against the FAK family kinases, providing valuable insights into therapeutic strategies for AS.
动脉粥样硬化（AS）是一种血管壁的慢性进行性炎症性疾病，也是心脑血管疾病的主要病理基础。粘着斑激酶（FAK）和富含脯氨酸的酪氨酸激酶2（Pyk2）是FAK家族激酶中两个高度同源的成员，在整合素信号传导中起关键作用。它们还作为支架蛋白，有助于调节细胞存活、细胞周期进程和细胞运动的细胞信号复合物的组装。研究表明，FAK家族激酶参与血管细胞的基因调控，该家族的异常表达与血管疾病的病理变化有关。这些发现确立了FAK家族激酶作为动脉粥样硬化病变中的关键信号介质，抑制其活性有可能减弱AS的病理进展。本综述强调了FAK家族激酶在与AS相关的异常血管平滑肌细胞增殖、内皮细胞功能障碍、炎症和脂质代谢中的不可或缺的作用。我们还总结了针对FAK家族激酶的治疗靶点，为AS的治疗策略提供了有价值的见解。
