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

J Clin Lipidol. Nov-Dec 2017;11(6):1361-1371. doi: 10.1016/j.jacl.2017.08.011. Epub 2017 Aug 26.

Abstract

Background: Hypertriglyceridemia increases risk for atherosclerotic cardiovascular disease and may contribute to atherosclerosis by changing circulating monocyte phenotypes. High-dose n-3 polyunsaturated 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.

Keywords: Atherosclerosis; Docosapentaenoic acid; Eicosapentaenoic acid; Hypertriglyceridemia; Monocytes; n-3 polyunsaturated fatty acids.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Atherosclerosis / blood
  • Atherosclerosis / drug therapy*
  • Atherosclerosis / pathology
  • CD11c Antigen / blood
  • CD36 Antigens / blood
  • Drug Combinations
  • Eicosapentaenoic Acid / administration & dosage*
  • Fatty Acids, Omega-3 / administration & dosage
  • Fatty Acids, Unsaturated / administration & dosage*
  • Female
  • Flow Cytometry
  • Humans
  • Hypertriglyceridemia / blood
  • Hypertriglyceridemia / drug therapy*
  • Hypertriglyceridemia / pathology
  • Male
  • Middle Aged
  • Monocytes / drug effects
  • Triglycerides / blood

Substances

  • CD11c Antigen
  • CD36 Antigens
  • Drug Combinations
  • Fatty Acids, Omega-3
  • Fatty Acids, Unsaturated
  • Triglycerides
  • Eicosapentaenoic Acid
  • docosapentaenoic acid