Regression of human coronary artery plaque is associated with a high ratio of (18‐hydroxy‐eicosapentaenoic acid + resolvin E1) to leukotriene B ₄

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.

Proresolving receptor tames inflammation in atherosclerosis

“…The results of the study by Arnardottir and Thul et al are congruent with prior studies demonstrating that loss of Erv1/ ChemR23 in atherosclerosis-prone mice worsens lesion development and that increasing RvE1 reduces atherosclerosis in both mice and rabbits (16,17). Moreover, artery disease (12). Mechanistic studies in animal models of atherosclerosis collectively demonstrate that increasing SPMs resolves plaque inflammation, improves efferocytosis, decreases necrotic cores, and increases markers of lesion stability (i.e., fibrous cap thickening; refs.…”

Encapsulation of Docosahexaenoic Acid Oil Substantially Improves the Oxylipin Profile of Rat Tissues

“…18-HEPE was also particularly concentrated in plasma of fat-1 mice compared with wild-type mice, and it was shown to protect against pulmonary metastasis of melanoma ( 74 ). More specifically, 18-HEPE was highly correlated with the coronary plaque regression on patients with coronary artery disease supplemented with high dose of n-3 PUFA for 30 months ( 75 ). Collectively in heart, the increase in PDx and 18-HEPE, together with the reduction of n-6 eicosanoids triggered by both DHA supply and oil encapsulation, emphasized the upgraded status on cardiac tissues on a short-term supplementation.…”

Safety and Preliminary Efficacy of a Novel Host-Modulatory Therapy for Reducing Gingival Inflammation

“…Peripheral blood serum samples were collected at baseline and 28 days via venipuncture, centrifuged at 2300 rpm and frozen at -80°C until analysis ( Supplementary Material and Supplementary Figure 1 ). LC-MS/MS-based metabololipidomics profiling was performed as previously described ( 34 , 35 ). Briefly, on the day of analysis, serum samples were thawed and methanol (9 volumes, -20°C, 60 min) containing 500 pg of deuterated internal standards d4-LTB 4 , d4-PGE 2 , d5-LXA 4 , d5-MaR2, d5-RvD2, and d8-5S-HETE were added to precipitate proteins and facilitate quantification of sample recovery.…”