Atherosclerosis Prevention Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.
Medical School, Islamic Azad University, Tehran Branch, Tehran, Iran.
Heart Fail Rev. 2021 Jan;26(1):205-213. doi: 10.1007/s10741-020-10001-9.
Therapeutic angiogenesis presents a potential approach for treating ischemic heart diseases especially in patients who are not appropriate candidates for traditional approaches of revascularization. This approach acts through inducing the neovascularization or maturation of pre-existing collateral vessels into functional arteries to bypass the blocked arteries and restore perfusion to ischemic myocardium. Successful stimulation of local angiogenesis can be established by the cross talk between stem cells, endothelial cells, and cardiomyocytes, which is mainly mediated by paracrine communication accompanied by secreted exosomes. Exosomes are extracellular vesicles carrying a complex of signaling molecules, such as microRNAs (miRs) that can modulate the function of recipient cells. Such particles have been indicated to exert cardioprotective role through providing signaling cues for angiogenesis, an effect ascribed mainly to their miRs content. Exosomal miRs-mediated therapeutic angiogenesis has been under drastic preclinical and clinical studies. In the current review, it was aimed to summarize pro-angiogenic exosomal miRs released by various cell types mediating angiogenesis, including stem cells, endothelial cells, and cardiomyocytes, which appear to exert a therapeutic effect on the myocardial ischemia. In brief, secreted exosomal miRs including miR-210, miR-23a-3p, miR-424, let-7f, miR-30b, miR-30c, miR-126, miR-21, miR-132, miR-130a-3p, miR-214, miR-378, miR-126, miR-133, and let-7b-5p could protect against myocardial ischemia through inducing cardiac angiogenesis and vascular regeneration resulting in the increase blood flow to ischemic myocardium.
治疗性血管生成为治疗缺血性心脏病提供了一种潜在的方法，特别是对于那些不适合传统血运重建方法的患者。这种方法通过诱导新生血管或使预先存在的侧支血管成熟为功能性动脉来绕过阻塞的动脉，从而恢复缺血心肌的灌注。通过干细胞、内皮细胞和心肌细胞之间的串扰，可以成功地刺激局部血管生成，这主要是通过旁分泌通讯伴随分泌的外泌体介导的。外泌体是携带信号分子复合物的细胞外囊泡，如可以调节受体细胞功能的 microRNAs（miRs）。这些颗粒通过为血管生成提供信号提示，发挥心脏保护作用，这种作用主要归因于它们的 miR 含量。外泌体 miR 介导的治疗性血管生成已经在剧烈的临床前和临床试验中进行了研究。在本综述中，旨在总结各种细胞类型释放的促血管生成外泌体 miR，包括干细胞、内皮细胞和心肌细胞，这些 miR 似乎对心肌缺血发挥了治疗作用。简而言之，包括 miR-210、miR-23a-3p、miR-424、let-7f、miR-30b、miR-30c、miR-126、miR-21、miR-132、miR-130a-3p、miR-214、miR-378、miR-126、miR-133 和 let-7b-5p 在内的分泌型外泌体 miR 可以通过诱导心脏血管生成和血管再生来保护心肌免受缺血，从而增加缺血心肌的血流量。
