Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease
Endothelial dysfunction as a possible link between C-reactive protein levels and cardiovascular disease
复制标题
DOI：
10.1042/cs20000013
复制
发表时间：
2000-05-01
期刊：
影响因子：
6
通讯作者：
Connell, JMC
中科院分区：
文献类型：
--
作者：
Cleland, SJ;Sattar, N;Connell, JMC
以C反应蛋白（CRP）血浆浓度升高为特征的低度慢性炎症与动脉粥样硬化性心血管疾病风险增加相关。内皮细胞活化是动脉粥样硬化形成的早期事件，先前的研究报道了内皮细胞活化的间接标志物与CRP浓度之间的相关性。因此，在本研究中，我们测量了CRP浓度（和瘦素浓度作为脂肪质量的指数）（平均年龄53 ± 8.1岁;体重指数27 ± 3.2 kg/m（2）;平均动脉血压101 +/- 9.0 mmHg），使用N-G-单甲基-L-精氨酸（L-NMMA;内皮NO合酶的底物抑制剂）和去甲肾上腺素（非特异性对照血管收缩剂）。在单变量分析中，CRP浓度与（i）L-NMMA输注期间前臂血流量（FBF）减少百分比（r = 0.85，P = 0.004）和（ii）血清瘦素浓度（r = 0.65，P = 0.05）相关。在多变量分析中，CRP浓度与FBF对L-NMMA的反应之间的关系在年龄和瘦素时仍然显著，（t = 2.65，P = 0.045），年龄和BMI（t = 3.69，P = 0.014），或年龄和低密度脂蛋白胆固醇+高密度脂蛋白胆固醇（t = 3.37，P = 0.044），均纳入回归模型。相反，FBF对去甲肾上腺素的反应与CRP浓度无显著相关。这些数据首次证明了低度慢性炎症和基础内皮NO合成（使用侵入性方法测量）之间的关系，并支持内皮功能障碍是炎症和心血管疾病之间关系的关键中间表型的概念。
Low-grade chronic inflammation, characterized by elevated plasma concentrations of C-reactive protein (CRP), is associated with an increased risk of atherosclerotic cardiovascular disease. Endothelial cell activation is an early event in atherogenesis, and previous studies have reported correlations between indirect markers of endothelial cell activation and CRP concentration. Therefore, in the present study, we measured CRP concentration (and leptin concentration as an index of fat mass) in nine healthy subjects (mean age 53+/-8.1 years; body mass index 27 +/- 3.2 kg/m(2); mean arterial blood pressure 101 +/- 9.0 mmHg) undergoing measurement of basal endothelial nitric oxide (NO) synthesis using intra-brachial infusions of N-G-monomethyl-L-arginine (L-NMMA; a substrate inhibitor of endothelial NO synthase) and noradrenaline (a nonspecific control vasoconstrictor). In univariate analysis, CRP concentration was correlated with (i) the percentage decrease in forearm blood flow (FBF) during L-NMMA infusion (r = 0.85, P = 0.004); and (ii) the serum leptin concentration (r = 0.65, P = 0.05). In multivariate analysis, the relationship between CRP concentration and the FBF response to L-NMMA remained significant when age and leptin (t = 2.65, P = 0.045), age and BMI (t = 3.69, P = 0.014), or age and low-density-lipoprotein-cholesterol plus high-density-lipoprotein-cholesterol (t = 3.37, P = 0.044), were included in regression models. In contrast, the response of FBF to noradrenaline was not significantly related to CRP concentration. These data demonstrate for the first time a relationship between low-grade chronic inflammation and basal endothelial NO synthesis (measured using an invasive method), and support the notion that endothelial dysfunction is a critical intermediate phenotype in the relationship between inflammation and cardiovascular disease.