P391Fractalkine (CX3CL1) in patients with stable coronary artery disease (CAD) with and without diabetes mellitus

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Background and purposeChemokine fractalkine and its receptor CX3CR1, are associated with atherosclerosis. Fractalkine exists in membrane-bound and soluble forms, functioning as adhesion molecule and chemoattractant. In vitro studies have shown increased expression of fractalkine in endothelial cells and vascular smooth muscle cells by inflammatory stimulus, and also by high glucose concentration. Fractalkine is found to be present in atherosclerotic plaques, especially in plaques from patients with diabetes mellitus (DM). Increased serum levels have been shown in unstable CAD- and in heart failure patients.The purpose of this study was to investigate whether CAD patients with DM have increased circulating levels of fractalkine compared to non-diabetics. Any relation between fractalkine and glucometabolic variables were further explored. Expression level of fractalkine and CX3CR1 in circulating leukocytes were also explored. MethodsSerum levels of fractalkine were analysed by ELISA method in 1001 patients with angiographically verified CAD, all included in the ASCET-trial*, of which 200 had DM. All patients were on aspirin, and 98% were using statin. Gene expression of CX3CR1 and fractalkine in circulating leukocytes (PAXGene tubes) (n=160), were performed on the ViiATM7 PCR system (Applied Biosystems).Results (medians (25, 75 percentiles))There were no significant difference in serum levels of fractalkine in patients with DM 653 pg/mL (556, 775) compared to patients without DM 646 pg/mL (553, 761), p=0.50. No significant correlations were found between fractalkine and glucose (r= -0.02, p=0.54), HbA1c (r=0.01, p=0.66) or CRP (r=-0.05, p=0.15). Fractalkine correlated with MCP-1 (r=0.20, p < 0.0001). Interestingly, smokers had significantly lower circulating levels compared to non-smokers (p < 0.0001). No difference in gene-expression of CX3CR1 in circulating leukocytes between patients with DM and patients without DM (p=0.13) was observed.ConclusionIn our population of stable CAD patients, no association between levels of soluble fractalkine and diabetes or glucometabolic variables could be demonstrated. Fractalkine correlated significantly with MCP-1 levels. No significant difference in gene-expression of CX3CR1 in circulating leukocytes between patients with and without DM was found.* Pettersen AA. Scand Cardiovasc J 2004, 38:353-6

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