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.
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 humanendotoxemia (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 humanatherosclerosis, particularly in acute coronary syndrome.
Authors: Michael Preuss; Inke R König; John R Thompson; Jeanette Erdmann; Devin Absher; Themistocles L Assimes; Stefan Blankenberg; Eric Boerwinkle; Li Chen; L Adrienne Cupples; Alistair S Hall; Eran Halperin; Christian Hengstenberg; Hilma Holm; Reijo Laaksonen; Mingyao Li; Winfried März; Ruth McPherson; Kiran Musunuru; Christopher P Nelson; Mary Susan Burnett; Stephen E Epstein; Christopher J O'Donnell; Thomas Quertermous; Daniel J Rader; Robert Roberts; Arne Schillert; Kari Stefansson; Alexandre F R Stewart; Gudmar Thorleifsson; Benjamin F Voight; George A Wells; Andreas Ziegler; Sekar Kathiresan; Muredach P Reilly; Nilesh J Samani; Heribert Schunkert Journal: Circ Cardiovasc Genet Date: 2010-10-05
Authors: Iryna Voloshyna; Sony Modayil; Michael J Littlefield; Elise Belilos; Kristina Belostocki; Lois Bonetti; Gary Rosenblum; Steven E Carsons; Allison B Reiss Journal: Exp Biol Med (Maywood) Date: 2013-09-02
Authors: David R Gibb; Sheinei J Saleem; Natalia S Chaimowitz; Joel Mathews; Daniel H Conrad Journal: Mol Immunol Date: 2011-01-13 Impact factor: 4.407
Authors: Iryna Voloshyna; Isaac Teboul; Michael J Littlefield; Nicolle M Siegart; George K Turi; Melissa J Fazzari; Steven E Carsons; Joshua DeLeon; Allison B Reiss Journal: Exp Biol Med (Maywood) Date: 2016-04-27
Authors: Andrew C Edmondson; Robert J Brown; Sekar Kathiresan; L Adrienne Cupples; Serkalem Demissie; Alisa Knodle Manning; Majken K Jensen; Eric B Rimm; Jian Wang; Amrith Rodrigues; Vaneeta Bamba; Sumeet A Khetarpal; Megan L Wolfe; Stephanie Derohannessian; Mingyao Li; Muredach P Reilly; Jens Aberle; David Evans; Robert A Hegele; Daniel J Rader Journal: J Clin Invest Date: 2009-03-16 Impact factor: 14.808