Impact of the renin-angiotensin-aldosterone-system on cardiovascular and renal complications in diabetes mellitus.
Impact of the renin-angiotensin-aldosterone-system on cardiovascular and renal complications in diabetes mellitus.
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DOI：
10.2174/1570161119999990001
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发表时间：
2010
影响因子：
4.5
通讯作者：
Tetsuya Hayashi;S. Takai;C. Yamashita
中科院分区：
文献类型：
--
作者：
Tetsuya Hayashi;S. Takai;C. Yamashita
糖尿病因其心血管并发症而成为发病率和死亡率的主要原因。已有研究表明，高血糖、高胰岛素血症和胰岛素抵抗、蛋白质糖基化、氧化应激、炎症等多种因素可能与糖尿病动脉粥样硬化的形成有关。糖尿病相关的代谢异常导致肾素-血管紧张素-醛固酮系统(RAAS)激活，继而血管紧张素II和醛固酮水平升高，这可能改变胰岛素信号通路，促进活性氧的形成，从而导致内皮功能障碍以及心血管疾病和肾脏疾病。血管紧张素II的合成不仅由血管紧张素转换酶催化，也由糜酶催化。近年来，由糜酶产生的血管紧张素II参与了血管增殖和动脉粥样硬化的研究。糜酶还激活基质金属蛋白酶-9，导致细胞外基质降解，促进心血管重塑。许多研究表明，血管紧张素-II受体拮抗剂可显著降低促炎介质水平，抑制氧化应激。在临床试验中，RAAS阻滞剂被发现可以延缓或预防2型糖尿病的发生，还可以预防糖尿病患者的心血管和肾脏事件。因此，抑制RAAS代表了高血压和糖尿病靶器官损害的一线治疗，以及防止心血管疾病和肾脏疾病的进展。本文综述了RAAS在糖尿病心血管和肾脏并发症中的作用。
Diabetes mellitus is a leading cause of morbidity and mortality because of its cardiovascular complications. It has been suggested that hyperglycemia, hyperinsulinemia and insulin resistance, glycation of proteins, oxidative stress, inflammation, and many other factors may be related to atherogenesis in diabetes. The metabolic abnormalities associated with diabetes lead to activation of the renin-angiotensin-aldosterone system (RAAS), with a subsequent increase of angiotensin II and aldosterone levels, which might alter the insulin signaling pathway and promote the formation of reactive oxygen species that induce endothelial dysfunction as well as cardiovascular disease and renal disease. Synthesis of angiotensin II is not only catalyzed by angiotensin-converting enzyme, but also by chymase. Recently, angiotensin II produced by chymase was reported to be involved in vascular proliferation and atherosclerosis. Chymase also activates matrix metalloproteinase-9, leading to extracellular matrix degradation, and promotes cardiovascular remodeling. Many studies have shown that angiotensin-II blockade significantly reduces the levels of proinflammatory mediators and suppresses oxidative stress. In clinical trials, RAAS blockade has been found to delay or prevent the onset of type 2 diabetes, and it also prevents cardiovascular and renal events in diabetic patients. Thus, RAAS inhibition represents first-line treatment for hypertensive and diabetic target organ damage, as well as preventing the progression of cardiovascular disease and kidney disease. This review presents the available information about the role of the RAAS in the cardiovascular and renal complications of diabetes.