Vita Joseph A, Keaney John F, Larson Martin G, Keyes Michelle J, Massaro Joseph M, Lipinska Izabella, Lehman Birgitta T, Fan Shuxia, Osypiuk Ewa, Wilson Peter W F, Vasan Ramachandran S, Mitchell Gary F, Benjamin Emelia J
Evans Memorial Department of Medicine, Boston University School of Medicine, Boston, Mass, USA.
Circulation. 2004 Dec 7;110(23):3604-9. doi: 10.1161/01.CIR.0000148821.97162.5E. Epub 2004 Nov 29.
In experimental studies, traditional risk factors and proinflammatory processes alter the regulatory functions of the vascular endothelium to promote atherosclerosis. These alterations include expression of leukocyte adhesion molecules and decreased bioavailability of endothelium-derived nitric oxide, an important regulator of vascular homeostasis and tone. The precise relations among risk factors, inflammation, and nitric oxide bioavailability remain uncertain.
To test the hypothesis that inflammation impairs endothelial function in humans, we measured brachial artery flow-mediated dilation, reactive hyperemia, and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), soluble intracellular adhesion molecule-1 (sICAM-1), and monocyte chemotactic protein-1 (MCP-1) in 2701 participants from the Framingham Study (mean age 61 years, 53% women). There were modest unadjusted inverse correlations between flow-mediated dilation and CRP, IL-6, and sICAM-1 (P<0.001 for all) that were rendered nonsignificant after accounting for traditional coronary risk factors. For reactive hyperemia, we observed inverse correlations with markers of inflammation in unadjusted models that were attenuated 57% to 74% after accounting for risk factors. However, partial correlations of CRP, IL-6, and sICAM-1 with reactive hyperemia remained significant.
Our observations are consistent with the hypothesis that risk factors induce a state of inflammation that impairs vascular function. For flow-mediated dilation, we found no evidence that inflammation has additional effects beyond those attributable to traditional risk factors. The incremental contribution of CRP, IL-6, and sICAM-1 to reactive hyperemia above and beyond known risk factors suggests that systemic inflammation may contribute to impaired vasomotor function in forearm microvessels.
在实验研究中，传统风险因素和促炎过程会改变血管内皮的调节功能，从而促进动脉粥样硬化。这些改变包括白细胞粘附分子的表达以及内皮源性一氧化氮生物利用度的降低，内皮源性一氧化氮是血管稳态和张力的重要调节因子。风险因素、炎症和一氧化氮生物利用度之间的确切关系仍不确定。
为了验证炎症会损害人类内皮功能这一假设，我们在弗雷明汉姆研究的2701名参与者（平均年龄61岁，53%为女性）中测量了肱动脉血流介导的舒张功能、反应性充血以及血清C反应蛋白（CRP）、白细胞介素-6（IL-6）、可溶性细胞间粘附分子-1（sICAM-1）和单核细胞趋化蛋白-1（MCP-1）的浓度。在未校正的情况下，血流介导的舒张功能与CRP、IL-6和sICAM-1之间存在适度的负相关（所有P<0.001），但在考虑传统冠状动脉风险因素后，这些相关性变得不显著。对于反应性充血，我们在未校正的模型中观察到与炎症标志物的负相关，在考虑风险因素后，这种相关性减弱了57%至74%。然而，CRP、IL-6和sICAM-1与反应性充血的偏相关性仍然显著。
我们的观察结果与风险因素诱导炎症状态进而损害血管功能这一假设一致。对于血流介导的舒张功能，我们没有发现证据表明炎症除了传统风险因素所导致的影响之外还有其他额外作用。CRP、IL-6和sICAM-1在已知风险因素之外对反应性充血的增量贡献表明，全身炎症可能导致前臂微血管血管舒缩功能受损。
