Effects of n-3 fatty acid treatment on monocyte phenotypes in humans with hypertriglyceridemia

被引:14
作者
Perrard, Xiao-Yuan Dai [1 ]
Lian, Zeqin [1 ]
Bobotas, George [2 ]
Dicklin, Mary R. [3 ]
Maki, Kevin C. [3 ]
Wu, Huaizhu [1 ,4 ]
机构
[1] Baylor Coll Med, Dept Med, Houston, TX 77030 USA
[2] Matinas BioPharma Inc, Bedminster, NJ USA
[3] Midwest Biomed Res, Ctr Metab & Cardiovasc Hlth, Glen Ellyn, IL USA
[4] Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA
关键词
Hypertriglyceridemia; Eicosapentaenoic acid; Docosapentaenoic acid; n-3 polyunsaturated fatty acids; Monocytes; Atherosclerosis; LOW-DENSITY-LIPOPROTEIN; OF-FUNCTION MUTATIONS; METABOLIC SYNDROME; FAMILIAL HYPERCHOLESTEROLEMIA; POSTPRANDIAL TRIGLYCERIDES; ATHEROSCLEROTIC PLAQUES; CARDIOVASCULAR-DISEASE; EICOSAPENTAENOIC ACID; DOCOSAPENTAENOIC ACID; DOCOSAHEXAENOIC ACID;
D O I
10.1016/j.jacl.2017.08.011
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
BACKGROUND: Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 poly-unsaturated fatty acids reduce blood triglyceride levels. Effects of triglyceride-lowering therapy on monocyte phenotypes are not well known. OBJECTIVE: We examined effects of n-3 polyunsaturated fatty acid treatments (eicosapentaenoic acid [EPA] plus docosapentaenoic acid [MAT9001] vs EPA ethyl esters [EPA-EE]) on monocyte phenotypes in individuals with hypertriglyceridemia. METHODS: Individuals with triglycerides 200 to 400 mg/dL were recruited. Subjects received 2 treatments in randomized order for 14 days each: MAT9001 and EPA-EE, at 4 g/d. At 2 days before the start of, and on the last day of, each treatment, nile red staining for lipids and phenotypes of each monocyte subset were examined by flow cytometry after an overnight fast and postprandially after a high-fat meal. RESULTS: Treatment with MAT9001 or EPA-EE reduced fasting triglyceride levels and decreased proportions of intermediate monocytes. Only MAT9001 decreased postprandial blood triglyceride levels, lowered fasting nile red levels, indicating less lipid in classical and intermediate monocytes, and reduced postprandial CD11c levels on nonclassical monocytes. MAT9001 and EPA-EE each reduced fasting and postprandial CD11c and CD36 levels on classical and intermediate monocytes and postprandial CCR5 levels on intermediate and nonclassical monocytes, with no significant differences between the 2 treatments. CONCLUSIONS: Treatment with MAT9001 in individuals with hypertriglyceridemia reduced fasting nile red staining for lipids in classical and intermediate monocytes. MAT9001 and EPA-EE each improved fasting and postprandial monocyte phenotypes, which could potentially help to protect against atherosclerosis. (C) 2017 National Lipid Association. All rights reserved.
引用
收藏
页码:1361 / 1371
页数:11
相关论文
共 53 条
[11]   Increased intermediate M1-M2 macrophage polarization and improved cognition in mild cognitive impairment patients on ω-3 supplementation [J].
Famenini, Sam ;
Rigali, Elizabeth A. ;
Olivera-Perez, Henry M. ;
Dang, Johnny ;
Chang, Michael To ;
Halder, Ramesh ;
Rao, Rammohan V. ;
Pellegrini, Matteo ;
Porter, Verna ;
Bredesen, Dale ;
Fiala, Milan .
FASEB JOURNAL, 2017, 31 (01) :148-160
[12]   Dietary docosahexaenoic acid suppresses T cell protein kinase Cθ lipid raft recruitment and IL-2 production [J].
Fan, YY ;
Ly, LH ;
Barhoumi, R ;
McMurray, DN ;
Chapkin, RS .
JOURNAL OF IMMUNOLOGY, 2004, 173 (10) :6151-6160
[13]   CD11c/CD18 Signals Very Late Antigen-4 Activation To Initiate Foamy Monocyte Recruitment during the Onset of Hypercholesterolemia [J].
Foster, Greg A. ;
Xu, Lu ;
Chidambaram, Alagu A. ;
Soderberg, Stephanie R. ;
Armstrong, Ehrin J. ;
Wu, Huaizhu ;
Simon, Scott I. .
JOURNAL OF IMMUNOLOGY, 2015, 195 (11) :5380-5392
[14]   On-chip phenotypic analysis of inflammatory monocytes in atherogenesis and myocardial infarction [J].
Foster, Greg A. ;
Gower, R. Michael ;
Stanhope, Kimber L. ;
Havel, Peter J. ;
Simon, Scott I. ;
Armstrong, Ehrin J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2013, 110 (34) :13944-13949
[15]   Development of Monocytes, Macrophages, and Dendritic Cells [J].
Geissmann, Frederic ;
Manz, Markus G. ;
Jung, Steffen ;
Sieweke, Michael H. ;
Merad, Miriam ;
Ley, Klaus .
SCIENCE, 2010, 327 (5966) :656-661
[16]   The omega-3 fatty acid docosahexaenoic acid favorably modulates the inflammatory pathways and macrophage polarization within aorta of LDLR-/- mice [J].
Gladine, Cecile ;
Zmojdzian, Monika ;
Joumard-Cubizolles, Laurie ;
Verny, Marie-Anne ;
Comte, Blandine ;
Mazur, Andrzej .
GENES AND NUTRITION, 2014, 9 (05)
[17]   CD11c/CD18 Expression Is Upregulated on Blood Monocytes During Hypertriglyceridemia and Enhances Adhesion to Vascular Cell Adhesion Molecule-1 [J].
Gower, R. Michael ;
Wu, Huaizhu ;
Foster, Greg A. ;
Devaraj, Sridevi ;
Jialal, Ishwarlal ;
Ballantyne, Christie M. ;
Knowlton, Anne A. ;
Simon, Scott I. .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2011, 31 (01) :160-+
[18]   Increased Cellular and Circulating Biomarkers of Oxidative Stress in Nascent Metabolic Syndrome [J].
Jialal, Ishwarlal ;
Devaraj, Sridevi ;
Adams-Huet, Beverley ;
Chen, Xinpu ;
Kaur, Harmeet .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2012, 97 (10) :E1844-E1850
[19]   Increased Toll-Like Receptor Activity in Patients With Metabolic Syndrome [J].
Jialal, Ishwarlal ;
Huet, Beverley A. ;
Kaur, Harmeet ;
Chien, Alexander ;
Devaraj, Sridevi .
DIABETES CARE, 2012, 35 (04) :900-904
[20]   Loss-of-Function Mutations in APOC3 and Risk of Ischemic Vascular Disease [J].
Jorgensen, Anders Berg ;
Frikke-Schmidt, Ruth ;
Nordestgaard, Borge G. ;
Tybjaerg-Hansen, Anne .
NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (01) :32-41