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大、小动脉内皮功能障碍。新的治疗方法。

Endothelial dysfunction in conduit arteries and in microcirculation. Novel therapeutic approaches.

机构信息

1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece.

1st Cardiology Department, Athens University Medical School, Hippokration Hospital, Greece.

出版信息

Pharmacol Ther. 2014 Dec;144(3):253-67. doi: 10.1016/j.pharmthera.2014.06.003. Epub 2014 Jun 11.

Abstract

The vascular endothelium not only is a single monolayer of cells between the vessel lumen and the intimal wall, but also plays an important role by controlling vascular function and structure mainly via the production of nitric oxide (NO). The so called "cardiovascular risk factors" are associated with endothelial dysfunction, that reduces NO bioavailability, increases oxidative stress, and promotes inflammation contributing therefore to the development of atherosclerosis. The significant role of endothelial dysfunction in the development of atherosclerosis emphasizes the need for efficient therapeutic interventions. During the last years statins, angiotensin-converting enzyme inhibitors, angiotensin-receptor antagonists, antioxidants, beta-blockers and insulin sensitizers have been evaluated for their ability to restore endothelial function (Briasoulis et al., 2012). As there is not a straightforward relationship between therapeutic interventions and improvement of endothelial function but rather a complicated interrelationship between multiple cellular and sub-cellular targets, research has been focused on the understanding of the underlying mechanisms. Moreover, the development of novel diagnostic invasive and non-invasive methods has allowed the early detection of endothelial dysfunction expanding the role of therapeutic interventions and our knowledge. In the current review we present the available data concerning the contribution of endothelial dysfunction to atherogenesis and review the methods that assess endothelial function with a view to understand the multiple targets of therapeutic interventions. Finally we focus on the classic and novel therapeutic approaches aiming to improve endothelial dysfunction and the underlying mechanisms.

摘要

血管内皮不仅是血管腔和内膜壁之间的单层细胞,还通过主要产生一氧化氮 (NO) 来控制血管功能和结构,发挥着重要作用。所谓的“心血管危险因素”与内皮功能障碍有关,内皮功能障碍会降低 NO 的生物利用度、增加氧化应激,并促进炎症,从而促进动脉粥样硬化的发展。内皮功能障碍在动脉粥样硬化发展中的重要作用强调了需要进行有效的治疗干预。在过去的几年中,他汀类药物、血管紧张素转换酶抑制剂、血管紧张素受体拮抗剂、抗氧化剂、β受体阻滞剂和胰岛素增敏剂已被评估其恢复内皮功能的能力 (Briasoulis 等人,2012)。由于治疗干预与内皮功能改善之间没有直接的关系,而是多个细胞和亚细胞靶标之间复杂的相互关系,因此研究的重点是理解潜在的机制。此外,新型诊断性侵入性和非侵入性方法的发展允许早期检测内皮功能障碍,从而扩大了治疗干预和我们的知识的作用。在当前的综述中,我们介绍了内皮功能障碍对动脉粥样硬化形成的贡献的现有数据,并回顾了评估内皮功能的方法,以了解治疗干预的多个靶标。最后,我们重点介绍了旨在改善内皮功能障碍和潜在机制的经典和新型治疗方法。

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