Isidori A M, Venneri M A, Fiore D
Department of Experimental Medicine, Sapienza University of Rome, Viale del Policlinico 155, 00161, Rome, Italy.
J Endocrinol Invest. 2016 Nov;39(11):1235-1246. doi: 10.1007/s40618-016-0502-0. Epub 2016 Jun 25.
The morbidity and mortality of diabetes mellitus are mostly attributed to cardiovascular complications. Despite tremendous advancement in glycemic control, anti-diabetic medications have failed to revert vascular impairment once triggered by the metabolic disorder. The angiogenic growth factors, Angiopoietin-1 (Ang1) and Angiopoietin-2 (Ang2), are crucial regulators of vessel formation and maintenance starting with embryonic development and continuing through life. In mature vessels, angiopoietins control vascular permeability, inflammation and remodeling. A crucial role of angiopoietins is to drive vascular inflammation from the active to the quiescent state, enabling restoration of tissue homeostasis. The mechanism is of particular importance for healing and repair after damage, two conditions typically impaired in metabolic disorders. There is an emerging body of evidences suggesting that the imbalance of Ang1 and Ang2 regulation, leading to an increased Ang2/Ang1 ratio, represents a culprit of the vascular alterations of patients with type-2 diabetes mellitus. Pharmacological modulation of Ang1 or Ang2 actions may help prevent or delay the onset of diabetic vascular complications by restoring vessel function, favoring tissue repair and maintaining endothelial quiescence. In this review, we present a summary of the role of Ang1 and Ang2, their involvement in diabetic complications, and novel therapeutic strategies targeting angiopoietins to ameliorate vascular health in metabolic disorders.
糖尿病的发病率和死亡率主要归因于心血管并发症。尽管血糖控制取得了巨大进展，但抗糖尿病药物一旦由代谢紊乱引发血管损伤，就无法使其恢复。血管生成生长因子血管生成素-1（Ang1）和血管生成素-2（Ang2）是从胚胎发育开始直至生命全程中血管形成和维持的关键调节因子。在成熟血管中，血管生成素控制血管通透性、炎症和重塑。血管生成素的一个关键作用是将血管炎症从活跃状态转变为静止状态，从而使组织内环境稳定得以恢复。该机制对于损伤后的愈合和修复尤为重要，而这两种情况在代谢紊乱中通常会受损。越来越多的证据表明，Ang1和Ang2调节失衡，导致Ang2/Ang1比值升高，是2型糖尿病患者血管改变的罪魁祸首。对Ang1或Ang2作用进行药理调节可能有助于通过恢复血管功能、促进组织修复和维持内皮静止来预防或延缓糖尿病血管并发症的发生。在本综述中，我们总结了Ang1和Ang2的作用、它们在糖尿病并发症中的参与情况，以及针对血管生成素的新型治疗策略，以改善代谢紊乱中的血管健康。
