Marino Franca, Guasti Luigina, Tozzi Matteo, Schembri Laura, Castiglioni Luana, Molteni Elisabetta, Piffaretti Gabriele, Castelli Patrizio, Cosentino Marco
Department of Clinical and Experimental Medicine, University of Insubria, Via Ottorino Rossi No. 9, 21100 Varese, Italy ; Center of Research in Medical Pharmacology, University of Insubria, Varese, Italy.
Int J Vasc Med. 2013;2013:412761. doi: 10.1155/2013/412761. Epub 2013 Feb 27.
Atherosclerosis is an inflammatory disease characterized by immunological activity, in which endothelial dysfunction represents an early event leading to subsequent inflammatory vascular damage. We investigated gene expression of the adhesion molecules (AMs) ICAM-1, VCAM-1, and β1-integrin in endothelial cells (ECs) isolated from venous blood (circulating EC, cEC) and purified from femoral plaques (pEC) obtained from 9 patients with peripheral artery disease (PAD) submitted to femoral artery thrombendarterectomy (FEA). In addition, in peripheral blood mononuclear cells (PBMCs) of the same subjects, we investigated gene expression of IFN-γ, IL-4, TGF-β, and IL-10. Patients were longitudinally evaluated 1 month before surgery, when statin treatment was established, at the time of surgery, and after 2 and 5 months. All AM mRNA levels, measured by means of real-time PCR, in cEC diminished during the study, up to 41-50% of initial levels at followup. AM mRNA expression was significantly higher in pEC than in cEC. During the study, in PBMCs, TGF-β and IL-10 mRNA levels remained unchanged while IFN-γ and IL-4 levels increased; however, the ratio IFN-γ/IL-4 showed no significant modification. In PAD patients, FEA and statin treatment induce a profound reduction of AM expression in cEC and affect cytokine mRNA expression in PBMCs.
动脉粥样硬化是一种以免疫活性为特征的炎症性疾病，其中内皮功能障碍是导致后续炎症性血管损伤的早期事件。我们研究了从9例接受股动脉血栓内膜切除术（FEA）的外周动脉疾病（PAD）患者的静脉血中分离（循环内皮细胞，cEC）并从股动脉斑块中纯化（斑块内皮细胞，pEC）的内皮细胞中黏附分子（AMs）细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）和β1整合素的基因表达。此外，在同一受试者的外周血单核细胞（PBMCs）中，我们研究了干扰素-γ（IFN-γ）、白细胞介素-4（IL-4）、转化生长因子-β（TGF-β）和白细胞介素-10（IL-10）的基因表达。在手术前1个月（此时他汀类药物治疗开始）、手术时、术后2个月和5个月对患者进行纵向评估。通过实时聚合酶链反应测量，在研究期间，cEC中所有AM mRNA水平均下降，随访时降至初始水平的41%-50%。pEC中AM mRNA表达明显高于cEC。在研究期间，PBMCs中TGF-β和IL-10 mRNA水平保持不变，而IFN-γ和IL-4水平升高；然而，IFN-γ/IL-4比值无明显变化。在PAD患者中，FEA和他汀类药物治疗可导致cEC中AM表达显著降低，并影响PBMCs中细胞因子mRNA表达。
