Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, Qin huai, Nanjing 210006, China.
Biomedical Instrument Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
Curr Pharm Des. 2018;24(4):451-464. doi: 10.2174/1381612824666171227220815.
Angiogenesis is described as a sprouting and growth process of new blood vessels from pre-existing vasculature. The relationship between angiogenesis and coronary artery disease (CAD) is double-sided. On one hand, angiogenesis within plaques is responsible for facilitating the growth and vulnerability of plaques by causing intraplaque hemorrhage and inflammatory cell influx, and overabundance of erythrocytes and inflammatory cells within a plaque probably causes plaque rupture, further leading to acute coronary syndrome. Therefore, inhibiting intraplaque angiogenesis has been considered as a potential therapeutic target for CAD. On the other hand, aiming at improving reperfusion to the ischemic myocardium in patients with CAD, angiogenesis promoting has been utilized as a therapeutic approach to expand myocardial microvascular network. Current strategies include direct administration of angiogenic growth factors (protein therapy), promoting angiogenic genes expression in vivo (gene therapy), and delivering stem cells (cell therapy) or exosomes (cell free therapy). This article will start by clarifying the basic concept of angiogenesis, interpret the mechanism of excessive intraplaque angiogenesis in atherosclerosis, and discuss its role in the growth and vulnerability of plaques. Then we will focus on the four distinct strategies of therapeutic angiogenesis. Despite promising animal studies and smallscale clinical trials of therapeutic angiogenesis in patients with ischemic heart disease, investigations have far not shown definite evidence of clinical efficacy. Hence, while acknowledging future work that remains to be done to validate the clinical results, we reviewed the critical challenges in this arena and highlighted the exciting progress that has occurred recently.
血管生成是指新血管从预先存在的脉管系统中发芽和生长的过程。血管生成与冠状动脉疾病（CAD）之间的关系是双向的。一方面，斑块内的血管生成通过导致斑块内出血和炎症细胞浸润，促进斑块的生长和脆弱性，斑块内过多的红细胞和炎症细胞可能导致斑块破裂，进一步导致急性冠状动脉综合征。因此，抑制斑块内血管生成已被认为是 CAD 的潜在治疗靶点。另一方面，为了改善 CAD 患者缺血心肌的再灌注，促进血管生成已被用作扩张心肌微血管网络的治疗方法。目前的策略包括直接给予血管生成生长因子（蛋白治疗）、促进体内血管生成基因的表达（基因治疗）以及输送干细胞（细胞治疗）或外泌体（无细胞治疗）。本文将首先阐明血管生成的基本概念，解释动脉粥样硬化中斑块内过度血管生成的机制，并讨论其在斑块生长和脆弱性中的作用。然后，我们将重点介绍四种不同的治疗性血管生成策略。尽管有前景的动物研究和缺血性心脏病患者治疗性血管生成的小规模临床试验，但研究远未显示出临床疗效的确凿证据。因此，虽然承认未来仍需要开展工作来验证临床结果，但我们回顾了该领域的关键挑战，并强调了最近发生的令人兴奋的进展。
