Kowalski J, Okopień B, Madej A, Zieliński M, Belowski D, Kalina Z, Herman Z S
Department of Clinical Pharmacology, Medical University of Silesia, 40-752 Katowice, 18 Medyków, Poland.
Eur J Clin Pharmacol. 2003 Jul;59(3):189-93. doi: 10.1007/s00228-003-0581-7. Epub 2003 May 17.
Monocytes that migrate into the arterial wall participate in the development and, eventually, rupture of the atherosclerotic plaque. The aim of this study was to evaluate the secretion of monocyte chemoattractant protein-1 (MCP-1) by monocytes from hyperlipidemic patients treated with hypolipidemic drugs, namely fenofibrate, simvastatin, or atorvastatin to determine what role is played by these drugs in the development and stabilization of the atherosclerotic plaque.
Fifty-four hyperlipidemic patients, who did not respond to a low-fat diet, were treated with fenofibrate, simvastatin, or atorvastatin (18 patients in each group) for 1 month. The control group included 18 normolipidemic, healthy, age-matched participants. Ten hyperlipidemic patients were effectively treated with hypolipidemic diet alone for 1 month. This group was compared with a control group of ten healthy subjects. To accurately evaluate the adhesion molecule levels, we excluded hyperlipidemic patients and control subjects with any inflammatory disease. Before and after treatment, monocytes were isolated from peripheral blood. After stimulation with lipopolysaccharide (LPS), MCP-1 secretion was measured by enzyme-linked immunosorbent assay (ELISA).
MCP-1 levels were significantly higher in hyperlipidemic patients than controls: 15.8+/-0.47, 16.7+/-0.23, and 14.9+/-0.45 compared with 12.36+/-0.42 ng/ml. Fenofibrate, atorvastatin, and simvastatin significantly decreased MCP-1 levels from 15.8+/-0.47 to 8.79+/-0.89, from 16.7+/-0.23 to 7.46+/-0.73, and from 14.9+/-0.45 to 10.3+/-0.8 ng/ml, respectively. In the diet-treated group of hyperlipidemic patients, the level of MCP-1 before therapy was significantly higher than in controls (16.89+/-0.31 vs 12.45+/-0.36 ng/ml). The diet therapy caused a significant decrease in levels of MCP-1 to 15.1+/-0.36 ng/ml. There was a correlation between the decreased levels of lipids and the decreased release of MCP-1 in the patients treated with hypolipemic drugs.
The drug-induced decrease in MCP-1 secretion in hyperlipidemic patients suggests that, apart from acting on lipids, the hypolipidemic drugs studied may directly inhibit the activity of monocytes.
迁移至动脉壁的单核细胞参与动脉粥样硬化斑块的形成，并最终导致斑块破裂。本研究旨在评估接受降血脂药物（即非诺贝特、辛伐他汀或阿托伐他汀）治疗的高脂血症患者单核细胞分泌单核细胞趋化蛋白-1（MCP-1）的情况，以确定这些药物在动脉粥样硬化斑块形成和稳定过程中所起的作用。
54例对低脂饮食无反应的高脂血症患者接受非诺贝特、辛伐他汀或阿托伐他汀治疗（每组18例），为期1个月。对照组包括18例血脂正常、健康且年龄匹配的参与者。10例高脂血症患者仅接受有效的低脂饮食治疗1个月。该组与10名健康受试者的对照组进行比较。为准确评估黏附分子水平，我们排除了患有任何炎症性疾病的高脂血症患者和对照受试者。治疗前后，从外周血中分离单核细胞。用脂多糖（LPS）刺激后，通过酶联免疫吸附测定（ELISA）测量MCP-1的分泌。
高脂血症患者的MCP-1水平显著高于对照组：分别为15.8±0.47、16.7±0.23和14.9±0.45，而对照组为12.36±0.42 ng/ml。非诺贝特、阿托伐他汀和辛伐他汀分别使MCP-1水平从15.8±0.47显著降至8.79±0.89、从16.7±0.23降至7.46±0.73以及从14.9±0.45降至10.3±0.8 ng/ml。在接受饮食治疗的高脂血症患者组中，治疗前MCP-1水平显著高于对照组（16.89±0.31对12.45±0.36 ng/ml）。饮食治疗使MCP-1水平显著降低至15.1±0.36 ng/ml。在接受降血脂药物治疗的患者中，血脂水平降低与MCP-1释放减少之间存在相关性。
高脂血症患者中药物诱导的MCP-1分泌减少表明，除了作用于血脂外，所研究的降血脂药物可能直接抑制单核细胞的活性。
