alexa CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans.
Medicine

Medicine

Internal Medicine: Open Access

Author(s): Lehrke M, Millington SC, Lefterova M, Cumaranatunge RG, Szapary P,

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Abstract OBJECTIVES: This study was designed to determine the association of CXCL16 with inflammation, atherosclerosis, and acute coronary syndromes. BACKGROUND: Vascular inflammation coincides with uptake of modified lipoproteins in the pathogenesis of atherosclerosis. CXCL16 is a protein that shares scavenger receptor function, promoting uptake of modified lipids, with the activities of an inflammatory chemokine. However, the role of CXCL16 in atherosclerosis remains uncertain. METHODS: The effect of inflammatory stimuli on CXCL16 gene and protein expression was studied in macrophages, mice, and humans, and the association of sol-CXCL16 with risk factors, atherosclerosis, and acute coronary syndromes was determined in humans. RESULTS: Endotoxin induction of CXCL16 in human macrophages was attenuated by aspirin, nuclear factor (NF)-kappa-B inhibition and peroxisome proliferator-activated receptor (PPAR)-gamma agonists. Experimental human endotoxemia (n = 6) led to an 8-fold increase in whole-blood CXCL16 messenger ribonucleic acid (p < 0.001) and a 1.7-fold increase in soluble (sol)-CXCL16 (p < 0.001), a cleaved active chemokine. Rosiglitazone-blocked endotoxin induced sol-CXCL16 in mice (p = 0.001), and pioglitazone (n = 28), compared to placebo (n = 28), lowered plasma sol-CXCL16 in metabolic syndrome subjects (p < 0.05). In a nested case-control study of acute and chronic coronary artery disease (n = 699), sol-CXCL16 levels correlated with inflammatory and metabolic risk factors and were associated with chronic coronary artery disease (odds ratio [OR] [95\% confidence interval], above vs. below median; 1.60 [1.01 to 2.58]; p = 0.04) and acute coronary syndromes (OR 2.52 [1.32 to 4.82], p = 0.005) following adjustment for established risk factors, medications, and C-reactive protein levels. CONCLUSIONS: Our findings suggest that CXCL16 may play a pro-inflammatory role in human atherosclerosis, particularly in acute coronary syndrome. This article was published in J Am Coll Cardiol and referenced in Internal Medicine: Open Access

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