Department of Nephrology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
J Atheroscler Thromb. 2011;18(11):958-65. doi: 10.5551/jat.8722. Epub 2011 Aug 27.
Fractalkine (CX3CL1), a chemokine, and its receptor CX3CR1 (expressed on T lymphocytes), have been shown to be abnormal in atherosclerosis. We investigated whether CX3CL1 levels and CX3CR1 expression were altered in patients with chronic kidney disease (CKD) and their association with common carotid artery intima-media thickness (CCA-IMT).
CX3CR1 expression on CD4(+) T cells was analyzed by flow cytometry in 62 healthy controls (HC) and 128 Stage III-V CKD subjects. Fractalkine and highly sensitive C-reactive protein (hsCRP) were analyzed by ELISA. CCA-IMT was measured by ultrasound.
Compared to HC, CKD patients exhibited a 2.5-fold increase in the CD4(+)CX3CR1(+) T cell population (14.8±0.6 vs 5.9±0.34%, p < 0.0001). The expression of CX3CR1 was largely restricted to those CD4(+) cells that lacked CD28 co-stimulatory molecule. Fractalkine (pg/mL) and hsCRP (µg/mL) levels were increased in CKD subjects (510.6±61.6 vs. 239.7±9.67, p =0.003, and 93.8± 5.3 vs. 48.4±6.8, p < 0.0001), as was the CCA-IMT (0.71±0.01 vs. 0.56±0.01 mm, p < 0.0001). There was a significant relationship between CD4(+)CX3CR1(+) T cells and fractalkine levels (r = 0.2, p =0.01). CCA-IMT correlated positively with CX3CR1(+) T cells (r =0.34, p < 0.0001), CD4(+) CX3CR1(+) T cells (r =0.39, p < 0.0001), CD4(+)CD28(null)CX3CR1(+) T cells (r =0.23, p =0.02), fractalkine (r =0.3, p =0.001), age (r =0.33, p < 0.0001) and diabetes (p =0.01). On multiple regression, only CD4(+)CX3CR1(+) T cells and the presence of diabetes continued to show an association with IMT (p < 0.0001 and 0.0029 respectively).
CKD subjects showed an increase in CD4(+)CX3CR1(+) T cell population, plasma fractalkine and IMT; the association of CD4(+)CX3CR1(+) T cells and plasma fractalkine with CCA-IMT indicates that the fractalkine-CX3CR1 pathway may be important in the development and/or progression of atherosclerosis in CKD.
趋化因子 fractalkine（CX3CL1）及其受体 CX3CR1（在 T 淋巴细胞上表达）在动脉粥样硬化中异常。我们研究了慢性肾脏病（CKD）患者的 CX3CL1 水平和 CX3CR1 表达是否发生改变及其与颈总动脉内膜中层厚度（CCA-IMT）的关系。
通过流式细胞术分析了 62 例健康对照（HC）和 128 例 III-V 期 CKD 患者的 CD4+T 细胞上的 CX3CR1 表达。通过 ELISA 分析 fractalkine 和高敏 C 反应蛋白（hsCRP）。通过超声测量 CCA-IMT。
与 HC 相比，CKD 患者的 CD4+CX3CR1+T 细胞群增加了 2.5 倍（14.8±0.6 与 5.9±0.34%，p < 0.0001）。CX3CR1 的表达主要局限于缺乏 CD28 共刺激分子的那些 CD4+细胞上。CKD 患者的 fractalkine（pg/mL）和 hsCRP（µg/mL）水平升高（510.6±61.6 与 239.7±9.67，p = 0.003 和 93.8±5.3 与 48.4±6.8，p < 0.0001），CCA-IMT 也升高（0.71±0.01 与 0.56±0.01mm，p < 0.0001）。CD4+CX3CR1+T 细胞与 fractalkine 水平之间存在显著关系（r = 0.2，p = 0.01）。CCA-IMT 与 CX3CR1+T 细胞呈正相关（r = 0.34，p < 0.0001）、CD4+CX3CR1+T 细胞（r = 0.39，p < 0.0001）、CD4+CD28（null）CX3CR1+T 细胞（r = 0.23，p = 0.02）、 fractalkine（r = 0.3，p = 0.001）、年龄（r = 0.33，p < 0.0001）和糖尿病（p = 0.01）。多元回归分析显示，只有 CD4+CX3CR1+T 细胞和糖尿病的存在与 IMT 持续相关（p < 0.0001 和 0.0029）。
CKD 患者的 CD4+CX3CR1+T 细胞群、血浆 fractalkine 和 IMT 增加；CD4+CX3CR1+T 细胞和血浆 fractalkine 与 CCA-IMT 的相关性表明，fractalkine-CX3CR1 通路可能在 CKD 患者动脉粥样硬化的发生和/或进展中起重要作用。
