Department of Pharmacology, Faculty of Dentistry, Mahidol University, 6 Yothe Road, Rajthevee, Bangkok 10400, Thailand.
Int J Mol Sci. 2013 Sep 13;14(9):18899-924. doi: 10.3390/ijms140918899.
Stroke is a major cause of mortality and disability worldwide. The main cause of stroke is atherosclerosis, and the most common risk factor for atherosclerosis is hypertension. Therefore, antihypertensive treatments are recommended for the prevention of stroke. Three angiotensin receptor blockers (ARBs), telmisartan, irbesartan and candesartan, inhibit the expression of the receptor for advanced glycation end-products (RAGE), which is one of the pleiotropic effects of these drugs. High mobility group box 1 (HMGB1) is the ligand of RAGE, and has been recently identified as a lethal mediator of severe sepsis. HMGB1 is an intracellular protein, which acts as an inflammatory cytokine when released into the extracellular milieu. Extracellular HMGB1 causes multiple organ failure and contributes to the pathogenesis of hypertension, hyperlipidemia, diabetes mellitus, atherosclerosis, thrombosis, and stroke. This is the first review of the literature evaluating the potential of three ARBs for the HMGB1-RAGE axis on stroke therapy, including prevention and acute treatment. This review covers clinical and experimental studies conducted between 1976 and 2013. We propose that ARBs, which inhibit the HMGB1/RAGE axis, may offer a novel option for prevention and acute treatment of stroke. However, additional clinical studies are necessary to verify the efficacy of ARBs.
中风是全世界范围内导致死亡和残疾的主要原因。中风的主要病因是动脉粥样硬化，而动脉粥样硬化最常见的危险因素是高血压。因此，推荐使用降压治疗来预防中风。三种血管紧张素受体阻滞剂（ARBs），替米沙坦、厄贝沙坦和坎地沙坦，可抑制晚期糖基化终产物受体（RAGE）的表达，这是这些药物的一种多效性作用。高迁移率族蛋白 B1（HMGB1）是 RAGE 的配体，最近被鉴定为严重脓毒症的致死性介质。HMGB1 是一种细胞内蛋白，当其释放到细胞外环境中时，可作为一种炎症细胞因子发挥作用。细胞外 HMGB1 可导致多器官衰竭，并有助于高血压、高血脂、糖尿病、动脉粥样硬化、血栓形成和中风的发病机制。这是第一篇评估三种 ARBs 对中风治疗中 HMGB1-RAGE 轴的潜在作用的文献综述，包括预防和急性治疗。本综述涵盖了 1976 年至 2013 年期间进行的临床和实验研究。我们提出，抑制 HMGB1/RAGE 轴的 ARBs 可能为中风的预防和急性治疗提供新的选择。然而，还需要进行更多的临床研究来验证 ARBs 的疗效。
