Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome
Nitric oxide modulates vascular inflammation and intimal hyperplasia in insulin resistance and the metabolic syndrome
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DOI：
10.1152/ajpheart.00982.2004
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Tzeng, E
中科院分区：
文献类型：
--
作者：
Barbato, JE;Zuckerbraun, BS;Tzeng, E
2型糖尿病(DM)和代谢综合征都以胰岛素抵抗为特征，都与动脉粥样硬化性血管疾病的加速形式和血管干预后不良结局相关。这些血管效应被认为源于炎症环境的加剧和一氧化氮(NO)的生物利用度降低。为了更好地了解这一过程，我们通过检测黏附分子的表达、炎细胞的募集和内膜增生的发展来表征肥胖Zucker大鼠的血管损伤反应。我们还评估了外源性NO抑制代谢综合征血管损伤后遗症的能力。对肥胖和瘦Zucker大鼠进行颈动脉球囊损伤。肥胖大鼠损伤后ICAM-1和P-选择素的表达较瘦大鼠升高。肥胖大鼠还表现为血管壁巨噬细胞浸润增加，新生内膜形成增加(内膜/中层=0.91vs.0.52，P=0.001)。腺病毒介导的诱导型一氧化氮合酶(INOS)基因转移后，ICAM-1、P-选择素、炎症细胞内流和氧化型低密度脂蛋白(LDL)受体的表达均明显低于单纯损伤。INOS基因转移还显著抑制了瘦肉动物和肥胖动物的增殖活性(54%和73%；P<；0.05)和新生内膜形成(53%和67%；P<；0.05)。面对肥胖和代谢综合征，血管损伤反应与黏附分子表达增加、炎细胞浸润、氧化型低密度脂蛋白受体表达和增殖相关。INOS基因转移能够有效地抑制这种高度的损伤反应，并在这种促炎环境中减少新生内膜的形成。
Type 2 diabetes mellitus (DM) and the metabolic syndrome, both characterized by insulin resistance, are associated with an accelerated form of atherosclerotic vascular disease and poor outcomes following vascular interventions. These vascular effects are thought to stem from a heightened inflammatory environment and reduced bioavailability of nitric oxide ( NO). To better understand this process, we characterized the vascular injury response in the obese Zucker rat by examining the expression of adhesion molecules, the recruitment of inflammatory cells, and the development of intimal hyperplasia. We also evaluated the ability of exogenous NO to inhibit the sequela of vascular injury in the metabolic syndrome. Obese and lean Zucker rats underwent carotid artery balloon injury. ICAM-1 and P-selectin expression were increased following injury in the obese animals compared with the lean rats. The obese rats also responded with increased macrophage infiltration of the vascular wall as well as increased neointima formation compared with their lean counterparts (intima/media = 0.91 vs. 0.52, P = 0.001). After adenovirus-mediated inducible NO synthase ( iNOS) gene transfer, ICAM-1, P-selectin, inflammatory cell influx, and oxidized low-density lipoprotein (LDL) receptor expression were all markedly reduced versus injury alone. iNOS gene transfer also significantly inhibited proliferative activity (54% and 73%; P < 0.05) and neointima formation (53% and 67%; P < 0.05) in lean and obese animals, respectively. The vascular injury response in the face of obesity and the metabolic syndrome is associated with increased adhesion molecule expression, inflammatory cell infiltration, oxidized LDL receptor expression, and proliferation. iNOS gene transfer is able to effectively inhibit this heightened injury response and reduce neointima formation in this proinflammatory environment.