Sardo Maria A, Campo Salvatore, Mandraffino Giuseppe, Saitta Carlo, Bonaiuto Antonio, Castaldo Maria, Cinquegrani Maurizio, Pizzimenti Giovanni, Saitta Antonino
Department of Internal Medicine, University of Messina, Messina, Italy.
Clin Chem. 2008 May;54(5):814-23. doi: 10.1373/clinchem.2007.095547. Epub 2008 Mar 13.
People with hypertension display an inflammatory pattern that includes increased plasma concentrations of monocyte chemoattractant protein 1 (MCP-1) and C-reactive protein (CRP) and enhanced expression of tissue factor (TF) mRNA in blood monocytes.
In this study, we investigated the relationship between CRP concentrations and TF and MCP-1 mRNA expression in unstimulated and lipopolysaccharide (LPS)-stimulated monocytes isolated from hypertensives with or without an increase in carotid intima-media thickness (IMT). We also investigated the expression of TF and MCP-1 mRNA and MCP-1 protein after in vitro addition of CRP to monocytes. We measured CRP (by immunonephelometry) and monocyte expression of TF and MCP-1 (by real-time PCR) in 80 untreated hypertensive patients without clinical cardiovascular disease (CVD) or additional risk factors for CVD compared with 41 controls. Based on IMT measured by carotid Doppler ultrasonography, patients were classified into the categories of normal (< or =1 mm) or abnormal (>1 mm). TF and MCP-1 mRNA and MCP-1 protein (by Western blotting) were measured after in vitro addition of CRP to monocytes from 10 randomized controls as well as 10 hypertensives with IMT < or =1 mm and 10 with IMT >1 mm.
CRP and TF and MCP-1 mRNA concentrations were significantly higher in IMT >1 mm hypertensives vs those with IMT < or =1 mm and controls. CRP had no effect on monocyte TF mRNA from either hypertensives or controls. CRP-stimulated monocytes from hypertensives, however, showed increased MCP-1 mRNA and protein expression compared with controls and LPS-stimulated cells.
Our findings suggest that the inflammatory response of blood monocytes plays an important role in the development of atherosclerosis and hypertension.
高血压患者呈现出一种炎症模式，包括血浆中单核细胞趋化蛋白1（MCP - 1）和C反应蛋白（CRP）浓度升高，以及血液单核细胞中组织因子（TF）mRNA表达增强。
在本研究中，我们调查了从有或无颈动脉内膜中层厚度（IMT）增加的高血压患者中分离出的未受刺激和脂多糖（LPS）刺激的单核细胞中，CRP浓度与TF和MCP - 1 mRNA表达之间的关系。我们还研究了体外向单核细胞中添加CRP后TF和MCP - 1 mRNA及MCP - 1蛋白的表达。我们测量了80例无临床心血管疾病（CVD）或CVD额外危险因素的未治疗高血压患者的CRP（通过免疫比浊法）以及单核细胞中TF和MCP - 1的表达（通过实时PCR），并与41名对照者进行比较。根据颈动脉多普勒超声测量的IMT，患者被分为正常（≤1 mm）或异常（>1 mm）类别。对来自10名随机对照者以及10名IMT≤1 mm和10名IMT>1 mm的高血压患者的单核细胞体外添加CRP后，测量TF和MCP - 1 mRNA及MCP - 1蛋白（通过蛋白质印迹法）。
与IMT≤1 mm的高血压患者及对照者相比，IMT>1 mm的高血压患者的CRP、TF和MCP - 1 mRNA浓度显著更高。CRP对高血压患者或对照者的单核细胞TF mRNA均无影响。然而，与对照者和LPS刺激的细胞相比，来自高血压患者的CRP刺激的单核细胞显示MCP - 1 mRNA和蛋白表达增加。
我们的研究结果表明，血液单核细胞的炎症反应在动脉粥样硬化和高血压的发展中起重要作用。
