Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.
Inflammation in arterial walls leads to coronary artery disease (CAD). Because specialized proresolving lipid mediators (SPMs; lipoxins, resolvins, and protectins) stimulate resolution of inflammation in animal models, we tested whether n-3 fatty acids impact SPM profiles in patients with CAD and promote clot remodeling. Six patients with stable CAD were randomly assigned to either treatment with daily 3.36 g Lovaza for 1 yr or without. Targeted lipid mediator-metabololipidomics showed that both groups had absence of resolvin D1 (RvD1), RvD2, RvD3, RvD5 and resolvin E1-all of which are present in healthy patients. Those not taking Lovaza had an absence of aspirin-triggered resolvin D3 (AT-RvD3) and aspirin-triggered lipoxin B4 (AT-LXB4). Lovaza treatment restored AT-RvD3 and AT-LXB4 and gave levels of RvD6 and aspirin-triggered protectin D1 (AT-PD1) twice as high (resolvin E2 ∼5 fold) as well as lower prostaglandins. Principal component analysis indicated positive relationships for patients with CAD who were receiving Lovaza with increased AT-RvD3, RvD6, AT-PD1, and AT-LXB4 SPMs identified in Lovaza-treated patients with CAD enhanced ∼50% at 1 nM macrophage uptake of blood clots. These results indicate that patients with CAD have lower levels and/or absence of specific SPMs that were restored with Lovaza; these SPMs promote macrophage phagocytosis of blood clots. Together, they suggest that low vascular SPMs may enable progression of chronic vascular inflammation predisposing to coronary atherosclerosis and to thrombosis.-Elajami, T. K., Colas, R. A., Dalli, J., Chiang, N., Serhan, C. N., Welty, F. K. Specialized proresolving lipid mediators in patients with coronary artery disease and their potential for clot remodeling.
Division of Cardiovascular Medicine, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA;
Tarec K
TK
Elajami
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Romain A
RA
Colas
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jesmond
J
Dalli
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nan
N
Chiang
Center for Experimental Therapeutics and Reperfusion Injury, Department of Anesthesiology, Perioperative and Pain Medicine, Harvard Institutes of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Charles N
CN
Serhan
Division of Cardiovascular Medicine, Department of Internal Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA; fwelty@bidmc.harvard.edu.
Francine K
FK
Welty
D000368:Aged; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism*; D004281:Docosahexaenoic Acids / Q000627:therapeutic use*; D004338:Drug Combinations; D015118:Eicosapentaenoic Acid / Q000627:therapeutic use*; D015525:Fatty Acids, Omega-3; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D050356:Lipid Metabolism; D044045:Lipoxins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use
D015415:Biomarkers; D004338:Drug Combinations; D015525:Fatty Acids, Omega-3; D044045:Lipoxins; D010975:Platelet Aggregation Inhibitors; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid; C405603:Omacor; D001241:Aspirin
inflammation; lipoxins; metabololipidomics; n-3 fatty acids; resolvins