Preferential Incorporation of Administered Eicosapentaenoic Acid Into Thin-Cap Atherosclerotic Plaques.

Abstract

OBJECTIVE:

n-3 polyunsaturated fatty acids, especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), have beneficial effects on atherosclerosis. Although specific salutary actions have been reported, the detailed distribution of n-3 polyunsaturated fatty acids in plaque and their relevance in disease progression are unclear. Our aim was to assess the pharmacodynamics of EPA and DHA and their metabolites in atherosclerotic plaques. Approach and Results: Apolipoprotein E-deficient (Apoe-/-) mice were fed a Western diet supplemented with EPA (1%, w/w) or DHA (1%, w/w) for 3 weeks. Imaging mass spectrometry analyses were performed in the aortic root and arch of the Apoe-/- mice to evaluate the distribution of EPA, DHA, their metabolites and the lipids containing EPA or DHA in the plaques. Liquid chromatography-mass spectrometry and histological analysis were also performed. The intima-media thickness of atherosclerotic plaque decreased in plaques containing free EPA and EPAs attached with several lipids. EPA was distributed more densely in the thin-cap plaques than in the thick-cap plaques, while DHA was more evenly distributed. In the aortic root, the distribution of total EPA level and cholesteryl esters containing EPA followed a concentration gradient from the vascular endothelium to the media. In the aortic arch, free EPA and 12-hydroxy-EPA colocalized with M2 macrophage.

CONCLUSIONS:

Administered EPA tends to be incorporated from the vascular lumen side and preferentially taken into the thin-cap plaque.

• Authors: Tomohito Sato, Makoto Horikawa, Shiro Takei, Fumiyoshi Yamazaki, Takashi K Ito, Takeshi Kondo, Takanobu Sakurai, Tomoaki Kahyo, Koji Ikegami, Shumpei Sato, Ryota Sato, Yasutaka Jinno, Hiroyuki Kawano, Satoko Naoe, Makoto Arita, Yukiyasu Kashiwagi, Mitsutoshi Setou
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 39 Issue 9 Pg. 1802-1816 (09 2019) ISSN: 1524-4636 [Electronic] United States
• PMID: 31366219 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol Esters
• Docosahexaenoic Acids
• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid
• Eicosapentaenoic Acid

Topics

• 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid (metabolism)
• Animals
• Cholesterol Esters (metabolism)
• Docosahexaenoic Acids (pharmacology)
• Eicosapentaenoic Acid (administration & dosage, metabolism, pharmacology)
• Macrophages (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Plaque, Atherosclerotic (drug therapy, metabolism)
• Tunica Intima (pathology)