Regression of human coronary artery plaque is associated with a high ratio of (18-hydroxy-eicosapentaenoic acid + resolvin E1) to leukotriene B4

FASEB J. 2021 Apr;35(4):e21448. doi: 10.1096/fj.202002471R.

Abstract

Inflammation in arterial walls leads to coronary artery disease (CAD). We previously reported that a high omega-3 fatty index was associated with prevention of progression of coronary atherosclerosis, a disease of chronic inflammation in the arterial wall. However, the mechanism of such benefit is unclear. The two main omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are precursors of specialized pro-resolving lipid mediators (SPMs)-resolvins and maresins-which actively resolve chronic inflammation. To explore whether SPMs are associated with coronary plaque progression, levels of SPMs and proinflammatory mediators (leukotriene B4 [LTB4 ] and prostaglandins) were measured using liquid chromatography-tandem mass spectrometry in 31 statin-treated patients with stable CAD randomized to either EPA and DHA, 3.36 g daily, or no EPA/DHA (control). Coronary plaque volume was measured by coronary computed tomographic angiography at baseline and at 30-month follow-up. Higher plasma levels of EPA+DHA were associated with significantly increased levels of two SPMs-resolvin E1 and maresin 1-and 18-hydroxy-eicosapentaenoic acid (HEPE), the precursor of resolvin E1. Those with low plasma EPA+DHA levels had a low (18-HEPE+resolvin E1)/LTB4 ratio and significant plaque progression. Those with high plasma EPA+DHA levels had either low (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque progression or high (18-HEPE+resolvin E1)/LTB4 ratios with significant plaque regression. These findings suggest that an imbalance between pro-resolving and proinflammatory lipid mediators is associated with plaque progression and potentially mediates the beneficial effects of EPA and DHA in CAD patients.

Trial registration: ClinicalTrials.gov NCT01624727.

Keywords: coronary plaque regression; inflammation; metabololipidomics; omega-3 fatty acids; resolvins.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Docosahexaenoic Acids / blood
  • Eicosapentaenoic Acid / analogs & derivatives*
  • Eicosapentaenoic Acid / blood*
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
  • Leukotriene B4 / blood*
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic / drug therapy*
  • Prostaglandins / blood*

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Prostaglandins
  • Leukotriene B4
  • Docosahexaenoic Acids
  • Eicosapentaenoic Acid
  • 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-eicosapentaenoic acid

Associated data

  • ClinicalTrials.gov/NCT01624727