Tucci Marco, Quatraro Cosima, Frassanito Maria Antonia, Silvestris Franco
DIMO, Department of Internal Medicine and Clinical Oncology, University of Bari, Italy.
J Hypertens. 2006 Jul;24(7):1307-18. doi: 10.1097/01.hjh.0000234111.31239.c3.
Arterial hypertension is recurrently associated with inflammation of the endothelium as an effect of the upregulation of functional molecules, including cytokines, adhesion molecules and chemokines. However, the role of monocyte chemoattractant protein-1 (MCP-1) in maintaining the inflammatory state of endothelial cells (EC) that leads to the progressive cardiovascular damage is unclear.
Here, we investigated the expression of MCP-1, its major cell source as well as recurrence of a defined polymorphism (-2518 MCP-1) apparently linked to endothelial damage in several diseases.
Serum MCP-1 was measured by enzyme-linked immunosorbent assay (ELISA) in 740 hypertensive patients, subdivided according to their individual organ damage. Expression of both MCP-1 and its receptor CCR2 was evaluated in circulating ECs and macrophages by flow cytometry and real-time reverse transcriptase-polymerase chain reaction (RT-PCR), while gene variants of MCP-1 were revealed by PCR.
Soluble MCP-1 was significantly elevated in patients with diffuse atheromasia. Furthermore, it was overexpressed by ECs activated to attract macrophages via the MCP-1/CCR2 pathway, whereas the -2518 MCP-1 polymorphism was correlated with atherosclerosis in most patients. CONCLUSIONS.: Overexpression of MCP-1 is predominant in hypertensive patients with atheromasia in the form of a defined polymorphism. Measurement of MCP-1 may thus reflect the degree of endothelial damage, while early detection of such a polymorphism may acquire a prognostic value in the development of atherosclerosis.
动脉高血压反复与内皮炎症相关，这是包括细胞因子、黏附分子和趋化因子在内的功能分子上调的结果。然而，单核细胞趋化蛋白-1（MCP-1）在维持导致进行性心血管损伤的内皮细胞（EC）炎症状态中的作用尚不清楚。
在此，我们研究了MCP-1的表达、其主要细胞来源以及一种明显与几种疾病中的内皮损伤相关的特定多态性（-2518 MCP-1）的复发情况。
通过酶联免疫吸附测定（ELISA）在740例高血压患者中测量血清MCP-1，这些患者根据其个体器官损伤情况进行了细分。通过流式细胞术和实时逆转录聚合酶链反应（RT-PCR）评估循环ECs和巨噬细胞中MCP-1及其受体CCR2的表达，而通过PCR揭示MCP-1的基因变体。
可溶性MCP-1在弥漫性动脉粥样硬化患者中显著升高。此外，通过MCP-1/CCR2途径被激活以吸引巨噬细胞的ECs使其过度表达，而-2518 MCP-1多态性在大多数患者中与动脉粥样硬化相关。结论：MCP-1的过度表达在患有以特定多态性形式存在的动脉粥样硬化的高血压患者中占主导地位。因此，MCP-1的测量可能反映内皮损伤程度，而这种多态性的早期检测可能在动脉粥样硬化的发展中具有预后价值。
