title: CXCL16 is a marker of inflammation, atherosclerosis, and acute coronary syndromes in humans.
abstract: OBJECTIVE
  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.
authors.affiliation: Institute of Diabetes, Obesity, and Metabolism, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Lehrke
authors.forename: Segan C
authors.initials: SC
authors.lastname: Millington
authors.forename: Martina
authors.initials: M
authors.lastname: Lefterova
authors.forename: Reshmaal Gomes
authors.initials: RG
authors.lastname: Cumaranatunge
authors.forename: Philippe
authors.initials: P
authors.lastname: Szapary
authors.forename: Robert
authors.initials: R
authors.lastname: Wilensky
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Rader
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Lazar
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
mesh_terms: D000208:Acute Disease; D000789:Angina, Unstable / Q000097:blood*; D000818:Animals; D050197:Atherosclerosis / Q000097:blood*; D015415:Biomarkers / Q000032:analysis; D002318:Cardiovascular Diseases / Q000097:blood*; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC / Q000032:analysis* / Q000096:biosynthesis; D003324:Coronary Artery Disease / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood*; D008264:Macrophages / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000097:blood*; D051116:Receptors, Scavenger / Q000032:analysis* / Q000096:biosynthesis; D013577:Syndrome
chemical_list: D015415:Biomarkers; C423727:CXCL16 protein, human; D000075743:Chemokine CXCL16; D019743:Chemokines, CXC; D051116:Receptors, Scavenger