Activation of protein kinase C isoforms and its impact on diabetic complications.
Activation of protein kinase C isoforms and its impact on diabetic complications.
复制标题
DOI：
10.1161/circresaha.110.217117
复制
发表时间：
2010-04-30
影响因子：
20.1
通讯作者：
King GL
中科院分区：
文献类型：
--
作者：
Geraldes P;King GL
心血管和微血管并发症对糖尿病患者的生活质量产生不利影响，并且是该人群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微血管和大血管并发症发展中最重要的代谢因素之一。存在几个突出的假说来解释高血糖症的不利影响。其中之一是蛋白激酶C（PKC）的高血糖症慢性激活，PKC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，例如渗透性、收缩性、细胞外基质合成、细胞生长和凋亡、血管生成、白细胞粘附以及细胞因子激活和抑制的增加。由不同PKC亚型（PKC-α、-β1/2和PKC-δ）引起的血管细胞稳态的这些扰动与影响大血管（动脉粥样硬化、心肌病）和小血管（视网膜病、肾病和神经病）并发症的病理学发展有关。已进行了使用PKC-β亚型抑制剂的临床试验，对糖尿病非增殖性视网膜病变、肾病和内皮功能障碍有一些积极的结果。本文综述了目前对PKC亚型如何引起糖尿病血管功能障碍和病变的认识。
Both cardio- and 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 micro- and 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 C (PKC), 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-α, -β1/2, and PKC-δ) are linked to the development of pathologies affecting large vessel (atherosclerosis, cardiomyopathy) and small vessel (retinopathy, nephropathy and neuropathy) complications. Clinical trials using a PKC-β isoform inhibitor have been conducted, with some positive results for diabetic nonproliferative retinopathy, nephropathy and endothelial dysfunction. This paper reviews current understanding of how PKC isoforms cause vascular dysfunctions and pathologies in diabetes.