Abstract 4093: CXCL16 is Marker of Inflammation, Atherosclerosis and Acute Coronary Syndromes in Humans (NPAM Young Investigator Awardee)
Background: Vascular inflammation coincides with uptake of modified lipoproteins in the pathogenesis of atherosclerosis. CXCL16 is a protein which shares scavenger receptor function, promoting uptake of modified lipids, with the activities of an inflammatory chemokine and adhesion molecule. 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 human atherosclerosis was determined. Repeated measures analysis of variance was applied to the data.
Results: Endotoxin and IFNγ induction of CXCL16 in human macrophages was attenuated by NF-κB inhibition and PPARγ agonists. Experimental human endotoxemia (n=6) led to 8-fold increase in whole blood CXCL16 mRNA (p<0.001) and 1.7 fold increase in plasma levels of sol-CXCL16 (p<0.001). Rosiglitazone blocked endotoxin induced sol-CXCL16 in mice (p=0.001) and Pioglitazone (3 months; n=28), compared to placebo (n=28), lowered plasma sol-CXCL16 levels in humans with the metabolic syndrome (p70% stenosis of 2 vessels), sol-CXCL16 levels correlated with inflammatory and metabolic risk factors and were associated (levels above versus below median) with chronic CAD [odds ratio (OR) (95% confidence interval); 1.70 (1.07–2.70); p=0.02] and acute coronary syndrome [OR 5.01 (2.70–9.40); p<0.001] following adjustment for established risk factors including plasma levels of C-reactive protein.
Conclusion: Our findings suggest that CXCL16 plays a pro-inflammatory role in human atherosclerosis and that it may represent a novel prognostic and therapeutic target in cardiovascular disease.