The Impact of Macrophage Insulin Resistance on Advanced Atherosclerotic Plaque Progression [2010;106:58–67] The RAGE Axis: A Fundamental Mechanism Signaling Danger to the Vulnerable Vasculature [2010;106:842–853] The Promise of Cell-Based Therapies for Di
The Impact of Macrophage Insulin Resistance on Advanced Atherosclerotic Plaque Progression [2010;106:58–67] The RAGE Axis: A Fundamental Mechanism Signaling Danger to the Vulnerable Vasculature [2010;106:842–853] The Promise of Cell-Based Therapies for Di
复制标题
DOI：
--
复制
发表时间：
2010
期刊：
影响因子：
--
通讯作者：
P. Geraldes;G. King
中科院分区：
文献类型：
--
作者：
P. Geraldes;G. King
心血管并发症和微血管并发症都对糖尿病患者的生活质量产生不利影响，是糖尿病患者死亡和发病的主要原因。糖尿病的心血管病变对微静脉、动脉和心肌有影响。高血糖被认为是糖尿病患者发生微血管和大血管并发症的重要代谢因素之一。有几个重要的假说可以解释高血糖的不良影响。其中之一是高血糖引起的蛋白激酶(PK)C的慢性激活，这是一种参与控制其他蛋白质功能的酶家族。PKC与血管改变有关，如通透性、收缩、细胞外基质合成、细胞生长和凋亡、血管生成、白细胞黏附以及细胞因子的激活和抑制。这些由不同的PKC亚型(PKC、1/2和PKC)引起的血管细胞动态平衡的紊乱与大血管(动脉粥样硬化、心肌病)和小血管(视网膜病变、肾病和神经病)并发症的发生有关。已经进行了使用PKCisform抑制剂的临床试验，在糖尿病非增殖性视网膜病变、肾病和内皮功能障碍方面取得了一些积极的结果。本文综述了目前对PKC亚型如何导致糖尿病血管功能障碍和病理的认识。(中国保监会决议2010；106：1319-1331。)
Both cardioand microvascular complications adversely affect the life quality of patients with diabetes and have been the leading cause of mortality and morbidity in this population. Cardiovascular pathologies of diabetes have an effect on microvenules, arteries, and myocardium. It is believed that hyperglycemia is one of the most important metabolic factors in the development of both microand macrovascular complications in diabetic patients. Several prominent hypotheses exist to explain the adverse effect of hyperglycemia. One of them is the chronic activation by hyperglycemia of protein kinase (PK)C, a family of enzymes that are involved in controlling the function of other proteins. PKC has been associated with vascular alterations such as increases in permeability, contractility, extracellular matrix synthesis, cell growth and apoptosis, angiogenesis, leukocyte adhesion, and cytokine activation and inhibition. These perturbations in vascular cell homeostasis caused by different PKC isoforms (PKC, 1/2, and PKC) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKCisoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy, and endothelial dysfunction. This article reviews present understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes. (Circ Res. 2010;106:1319-1331.)