Semaan H B, Gurbel P A, Anderson J L, Muhlestein J B, Carlquist J F, Horne B D, Serebruany V L
Department of Medicine, Union Memorial Hospital, Baltimore, Maryland, USA.
J Cardiovasc Pharmacol. 2000 Oct;36(4):533-7. doi: 10.1097/00005344-200010000-00018.
In patients with coronary artery disease (CAD), azithromycin therapy is associated with decreased cytokine levels and overall reduction of inflammation. Chlamydia pneumoniae (C.Pn) is a common pathogen that may be an important factor in the development and progression of atherosclerosis. Cell-adhesion molecules have an important role in recruitment of inflammatory cells during plaque development and are expressed by endothelial cells on activation. We sought to define the effect of treatment with azithromycin on circulating levels of soluble vascular cell-adhesion molecule (VCAM-I), intercellular adhesion molecule (ICAM-1), and E-selectin in patients with CAD. Plasma concentrations of VCAM-1, ICAM-1, and E-selectin were measured in 40 patients with documented CAD and a positive (> or = 1:16) immunoglobulin G (IgG) titer against C.Pn, 20 subjects with normal coronary arteries, and 14 healthy volunteers. Patients were assigned randomly to receive either 500 mg/wk of azithromycin or placebo for 3 months. Serum samples were obtained at baseline, at 3 months, and during the follow-up visit at 6 months. Patients with documented CAD exhibited elevation of VCAM-1 (535 +/- 227 ng/ ml; p = 0.0001) and E-selectin (69 +/- 29 ng/ml; p = 0.006), but not ICAM-1 (321 +/- 65 ng/ml) concentrations as compared with the patients with angiographically proven normal coronary arteries (252 +/- 80; 50 +/- 22; and 311 +/- 40 ng/ml) and healthy controls (110 +/- 18; 29 +/- 2; and 238 +/- 47 ng/ml, respectively). Prolonged treatment with azithromycin did not significantly affect the plasma levels of soluble VCAM-1, ICAM-1, and E-selectin. Soluble markers of endothelial activation are markedly increased in patients with documented CAD as compared with those with normal coronary arteries and healthy controls. Despite substantial heterogeneity in plasma E-selectin, ICAM-1, and VCAM-1 levels, long-term azithromycin treatment did not affect plasma levels of these adhesion molecules, indicative of endothelial activation, over a period of 6 months.
在冠心病（CAD）患者中，阿奇霉素治疗与细胞因子水平降低及炎症的整体减轻相关。肺炎衣原体（C.Pn）是一种常见病原体，可能是动脉粥样硬化发生和发展的重要因素。细胞黏附分子在斑块形成过程中对炎症细胞的募集起重要作用，并在内皮细胞激活时表达。我们试图确定阿奇霉素治疗对CAD患者循环中可溶性血管细胞黏附分子（VCAM-1）、细胞间黏附分子（ICAM-1）和E-选择素水平的影响。对40例有记录的CAD且抗C.Pn免疫球蛋白G（IgG）滴度呈阳性（≥1:16）的患者、20例冠状动脉正常的受试者以及14名健康志愿者，测定其血浆中VCAM-1、ICAM-1和E-选择素的浓度。患者被随机分配接受每周500mg阿奇霉素或安慰剂治疗3个月。在基线、3个月时以及6个月的随访时采集血清样本。与冠状动脉造影证实正常的患者（分别为252±80、50±22和311±40ng/ml）及健康对照（分别为110±18、29±2和238±47ng/ml）相比，有记录的CAD患者的VCAM-1（535±227ng/ml；p = 0.0001）和E-选择素（69±29ng/ml；p = 0.006）浓度升高，但ICAM-1（321±65ng/ml）浓度未升高。阿奇霉素的长期治疗对可溶性VCAM-1、ICAM-1和E-选择素的血浆水平无显著影响。与冠状动脉正常的患者和健康对照相比，有记录的CAD患者内皮激活的可溶性标志物明显升高。尽管血浆E-选择素、ICAM-1和VCAM-1水平存在很大异质性，但在6个月的时间里，长期阿奇霉素治疗并未影响这些指示内皮激活的黏附分子的血浆水平。
