Rosenson Robert S, Wolff David, Tangney Christine C
Preventive Cardiology Center, Northwestern University, The Feinberg School of Medicine, 201 East Huron Street, Galter Pavilion, Chicago, IL 60611, U.S.A.
Clin Sci (Lond). 2004 Feb;106(2):215-7. doi: 10.1042/CS20030291.
ICAM-1 (intercellular cell-adhesion molecule-1) and VCAM-1 (vascular cell-adhesion molecule-1) are cell-adhesion molecules that have an essential role in monocyte recruitment. In the present study we have investigated (i) whether statins reduce soluble levels of ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1), and the relationship between resistance of LDL (low-density lipoprotein) to in vitro oxidation and sICAM-1 and sVCAM-1 levels. Whole blood samples were obtained from 55 healthy non-smoking adults (aged 35-65 years) with moderate (LDL-cholesterol, 3.4-4.9 mmol/l) hypercholesterolaemia participating in a randomized double-blinded, 8-week trial comparing pravastatin (40 mg), simvastatin (20 and 80 mg) and placebo. sICAM-1 levels (means+/-S.D.) increased slightly from 12.2+/-4.2 to 13.6+/-4.2 ng/ml with statin therapy, whereas, among placebo-assigned subjects, levels were unchanged (11.8+/-5.0 and 11.8+/-3.9 ng/ml). sVCAM-1 increased from 18.9+/-10.1 to 21.1+/-7.4 ng/ml among those on active therapy and slightly declined with placebo assignment (19.8+/-8.8 to 19.4+/-6.4 ng/ml). Lag times increased with statin therapy from 74.3+/-39.8 min to 98.3+/-57.8 min ( P =0.003), and were unchanged in the placebo group (from 103.1+/-61.1 to 90.8+/-65.9 min; P =0.48). There were no significant changes between statin and placebo therapy for sICAM-1, sVCAM-1 or lag times ( P =0.09, 0.16 and 0.067 respectively). Changes in sICAM-1 and sVCAM-1 were not correlated with the change in lag times. In contrast with the known effects of oxidized LDL on gene activation of ICAM-1 and VCAM-1, lag times did not correlate with sICAM-1 and sVCAM-1. Statin therapy improved lag times, but has no effect on sICAM-1 or sVCAM-1 levels.
细胞间黏附分子-1（ICAM-1）和血管细胞黏附分子-1（VCAM-1）是在单核细胞募集中起关键作用的细胞黏附分子。在本研究中，我们调查了：（i）他汀类药物是否会降低ICAM-1（sICAM-1）和VCAM-1（sVCAM-1）的可溶性水平，以及低密度脂蛋白（LDL）对体外氧化的抗性与sICAM-1和sVCAM-1水平之间的关系。从55名年龄在35至65岁、患有中度（LDL胆固醇水平为3.4至4.9 mmol/l）高胆固醇血症的健康非吸烟成年人中采集全血样本，这些人参与了一项随机双盲、为期8周的试验，该试验比较了普伐他汀（40 mg）、辛伐他汀（20 mg和80 mg）与安慰剂。接受他汀类药物治疗时，sICAM-1水平（均值±标准差）从12.2±4.2 ng/ml略有升高至13.6±4.2 ng/ml，而在分配接受安慰剂的受试者中，水平未发生变化（分别为11.8±5.0 ng/ml和11.8±3.9 ng/ml）。接受活性治疗的受试者中，sVCAM-1从18.9±10.1 ng/ml升高至21.1±7.4 ng/ml，而接受安慰剂治疗的受试者中则略有下降（从19.8±8.8 ng/ml降至19.4±6.4 ng/ml）。接受他汀类药物治疗时，延滞时间从74.3±39.8分钟增加至98.3±57.8分钟（P = 0.003），而在安慰剂组中则未发生变化（从103.1±61.1分钟降至90.8±65.9分钟；P = 0.48）。他汀类药物治疗与安慰剂治疗在sICAM-1、sVCAM-1或延滞时间方面无显著变化（P分别为0.09、0.16和0.067）。sICAM-1和sVCAM-1的变化与延滞时间的变化不相关。与氧化型LDL对ICAM-1和VCAM-1基因激活的已知作用相反，延滞时间与sICAM-1和sVCAM-1不相关。他汀类药物治疗改善了延滞时间，但对sICAM-1或sVCAM-1水平无影响。
