Abstract：
Advanced atherosclerosis is linked to plaque instability, which can result in rupture and the onset of a heart attack. Evidence gathered from human atheroma plaques indicates that intraplaque neovascularization poses a risk to plaque stability and may lead to plaque hemorrhage. Hence, targeting the neovascularization within the atheroma plaque has the potential to mitigate the plaque\'s vulnerability. While neovascularization has been extensively explored in the context of cancer, research on pharmacological inhibition of this phenomenon in atherosclerosis remains limited. This systematic review aimed to comprehensively assess current and emerging pharmacological interventions for inhibiting intraplaque neovascularization in preclinical settings. Electronic databases (Web of Science, PubMed, Scopus, and Ovid) were searched from January 2013 until February 1, 2024. Preclinical studies reporting the effect of any pharmacological interventions targeting intraplaque neovascularization were included. A total of 10 articles involving in vivo animal studies were eligible for inclusion, with five of them incorporating in vitro experiments to complement their in vivo findings. The pharmacological interventions studied were axitinib, ghrelin, K5, rosuvastatin, atorvastatin, 3PO, everolimus, melatonin, Si-Miao-Yong-A, and protocatechuic aldehyde. All the interventions showed a positive impact in inhibiting intraplaque neovascularization in various atherosclerotic animal models through various signaling pathways. This review provides valuable insights into pharmacological approaches to attenuate intraplaque neovascularization that could serve as a promising therapeutic avenue to enhance plaque stability.
摘要：
晚期动脉粥样硬化与斑块不稳定有关,这可能导致破裂和心脏病发作。从人类动脉粥样硬化斑块收集的证据表明，斑块内新生血管形成对斑块稳定性有风险，并可能导致斑块出血。因此，靶向动脉粥样硬化斑块内的新生血管有可能减轻斑块的易损性。虽然在癌症的背景下已经广泛探索了新血管形成，在动脉粥样硬化中对这种现象的药理抑制的研究仍然有限。本系统综述旨在全面评估在临床前环境中抑制斑块内新生血管形成的当前和新兴药物干预措施。电子数据库(WebofScience，PubMed,Scopus,和Ovid)从2013年1月至2024年2月1日进行搜索。包括报告针对斑块内新生血管形成的任何药物干预措施的效果的临床前研究。共有10篇涉及体内动物研究的文章符合纳入条件,其中五个纳入体外实验，以补充他们的体内发现。研究的药物干预措施是阿西替尼，ghrelin,K5，瑞舒伐他汀，阿托伐他汀,3PO,依维莫司,褪黑激素,思苗永安,和原儿茶醛。在各种动脉粥样硬化动物模型中，所有干预措施均显示出通过各种信号通路抑制斑块内新生血管形成的积极影响。这篇综述为减轻斑块内新生血管形成的药理学方法提供了有价值的见解，这些方法可以作为增强斑块稳定性的有希望的治疗途径。
