The importance of endothelin-1 for microvascular dysfunction in diabetes.
The importance of endothelin-1 for microvascular dysfunction in diabetes.
复制标题
DOI：
10.2147/vhrm.s3920
复制
发表时间：
2008
影响因子：
2.9
通讯作者：
Kalani M
中科院分区：
文献类型：
--
作者：
Kalani M
大多数糖尿病晚期并发症，如视网膜病变、肾病和神经病变，其基础是微血管功能紊乱。无论研究的器官如何，糖尿病都存在微循环的结构和功能变化，并且发病机制复杂。以内皮源性血管扩张物质和血管收缩物质失衡为特征的内皮功能障碍在糖尿病微血管病的发病机制中发挥着重要作用。在糖尿病患者中发现内皮素-1（ET-1）（一种有效的血管收缩肽）的循环水平增加，并且已证明2型糖尿病患者中血浆ET-1水平与微血管病变之间呈正相关。除了其直接的血管收缩作用外，ET-1水平升高可能通过抑制一氧化氮（NO）的产生而导致内皮功能障碍。血管内皮功能障碍可能先于胰岛素抵抗，尽管胰岛素抵抗综合征的特征包括对内皮功能有负面影响的因素。此外，ET-1诱导胰岛素敏感性降低，并可能参与代谢综合征的发展。在下文中，讨论了ET-1促进糖尿病微血管病变发展的机制以及选择性ETA受体拮抗剂的潜在有益作用。
Most of the late diabetic complications such as retinopathy, nephropathy, and neuropathy, have their basis in disturbed microvascular function. Structural and functional changes in the micro-circulation are present in diabetes mellitus irrespective of the organ studied, and the pathogenesis is complex. Endothelial dysfunction, characterized by an imbalance between endothelium-derived vasodilator and vasoconstrictor substances, plays an important role in the pathogenesis of diabetic microangiopathy. Increased circulating levels of endothelin-1 (ET-1), a potent vasoconstrictor peptide, has been found in patients with diabetes, and a positive correlation between plasma ET-1 levels and microangiopathy in patients with type 2 diabetes has been demonstrated. In addition to its direct vasoconstrictor effects, enhanced levels of ET-1 may contribute to endothelial dysfunction through inhibitory effects on nitric oxide (NO) production. Vascular endothelial dysfunction may precede insulin resistance, although the feature of insulin resistance syndrome includes factors that have negative effects on endothelial function. Furthermore, ET-1 induces a reduction in insulin sensitivity and may take part in the development of the metabolic syndrome. In the following, the mechanisms by which ET-1 contributes to the development of diabetic microangiopathy and the potentially beneficial effect of selective ETA receptor antagonists are discussed.