New aspects in the pathogenesis of diabetic atherothrombosis
New aspects in the pathogenesis of diabetic atherothrombosis
复制标题
DOI：
10.1016/j.jacc.2004.07.060
复制
发表时间：
2004-12-21
影响因子：
24
通讯作者：
Fuster, V
中科院分区：
文献类型：
--
作者：
Moreno, PR;Fuster, V
由于肥胖、炎症和高血糖症的相互作用，糖尿病在全球范围内不断增加。激活的免疫和细胞因子产生导致胰岛素抵抗和代谢综合征的其他成分，建立糖尿病和动脉粥样硬化之间的联系。高血糖诱导的内皮功能障碍是由氧化应激增加介导的，氧化应激是糖尿病动脉粥样硬化实验模型中外膜炎症和血管新生血管形成的促进剂。最近的研究已经证实了人类糖尿病动脉粥样硬化中炎症、新生血管和斑块内出血的增加。这种炎症性微血管病变过程与斑块破裂独立相关，导致冠状动脉血栓形成。组织因子是凝血级联反应最有效的触发因子，在血糖控制不佳的糖尿病患者中增加。循环组织因子微粒也与斑块巨噬细胞的凋亡相关，从而关闭炎症、斑块破裂和血液血栓形成之间的联系。负责清除游离胆固醇的高密度脂蛋白在胰岛素抵抗和糖尿病患者中减少。高密度脂蛋白治疗导致斑块巨噬细胞显著减少，平滑肌细胞增加。这些有益作用可能是重组载脂蛋白A-I Milano/磷脂复合物治疗患者冠状动脉斑块稳定的原因。最后，过氧化物酶体增殖物激活受体（PPARs）现在被认为是动脉粥样硬化的核转录调节因子。已经鉴定了三个亚家族，包括PPAR-alpha、-delta和-gamma，在脂质代谢、斑块炎症、粘附分子和细胞因子的表达以及基质金属蛋白酶的调节中具有关键作用。多项实验研究已经证明了使用PPAR-gamma激动剂的斑块稳定性，这是一组在治疗糖尿病动脉粥样硬化方面前景广阔的药物。(C)2004年，美国心脏病学会基金会。
Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis. (C) 2004 by the American College of Cardiology Foundation.