Hyperlipidemia Research Center, Department of Biochemistry, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Endocr Metab Immune Disord Drug Targets. 2022;22(12):1191-1200. doi: 10.2174/1871530322666220606090801.
Atherosclerosis is a chronic inflammatory disease of the arteries characterized by the accumulation of inflammatory cells in the arterial wall. Hypertension, dyslipidemia, and hyperglycemia are major risk factors of atherosclerosis. Rho-associated protein kinase (ROCK), a serine/threonine kinase, is a downstream effector of the small GTPase RhoA. ROCK is involved in different stages of atherosclerosis. Accumulating evidence has demonstrated that ROCK signaling plays vital roles in various cellular functions, such as contraction, migration, and proliferation of smooth muscle cells. Dysregulation of the ROCK pathway is associated with atherosclerosis and hypertension. Experimental studies have shown that ROCK inhibitors may have favorable effects in ameliorating atherosclerosis. ROCK signaling has a role in proteoglycan synthesis through transactivation of the TGF-β receptor Type I (TβRI) mediated by G-protein-coupled receptor (GPCR) agonists (endothelin-1, angiotensin II and …), and ROCK inhibitors could decrease proteoglycan synthesis and atherosclerotic plaque formation. Based on the hypothesis that targeting ROCK pathway may be effective in ameliorating atherosclerosis, we suggest that ROCK inhibitors may have a potential therapeutic role in inhibition or slowing atherogenesis. However, for this hypothesis more research is needed.
动脉粥样硬化是一种慢性炎症性疾病，其特征是动脉壁中炎症细胞的积累。高血压、血脂异常和高血糖是动脉粥样硬化的主要危险因素。Rho 相关蛋白激酶（ROCK）是一种丝氨酸/苏氨酸激酶，是小 GTP 酶 RhoA 的下游效应物。ROCK 参与动脉粥样硬化的不同阶段。越来越多的证据表明，ROCK 信号通路在平滑肌细胞的收缩、迁移和增殖等多种细胞功能中发挥着重要作用。ROCK 通路的失调与动脉粥样硬化和高血压有关。实验研究表明，ROCK 抑制剂可能在改善动脉粥样硬化方面具有良好的效果。ROCK 信号通路通过 G 蛋白偶联受体（GPCR）激动剂（内皮素-1、血管紧张素 II 等）介导的转化生长因子-β 受体 I（TβRI）的转激活，在蛋白聚糖合成中起作用，ROCK 抑制剂可减少蛋白聚糖合成和动脉粥样硬化斑块形成。基于靶向 ROCK 通路可能有效改善动脉粥样硬化的假设，我们认为 ROCK 抑制剂在抑制或减缓动脉粥样硬化形成方面可能具有潜在的治疗作用。然而，对于这一假设还需要更多的研究。
