Anti-Atherosclerotic Effects of Dihomo-γ-Linolenic Acid in ApoE-Deficient Mice

• Published in: Journal of Atherosclerosis and Thrombosis 2009, Vol.16(4), pp.480-489
• Main Authors: Takai, Shinji, Jin, Denan, Kawashima, Hiroshi, Kimura, Maki, Shiraishi-Tateishi, Akiko, Tanaka, Takao, Kakutani, Saki, Tanaka, Kazuhiko, Kiso, Yoshinobu, Miyazaki, Mizuo
• Format: Article
• Language: English
• Subjects: 8,11,14-Eicosatrienoic Acid - administration & dosage; 8,11,14-Eicosatrienoic Acid - pharmacology; 8,11,14-Eicosatrienoic Acid - therapeutic use; Alprostadil - biosynthesis; Animals; ApoE-defocient mice; Apolipoproteins E - deficiency; Atherosclerosis; Atherosclerosis - drug therapy; Atherosclerosis - prevention & control; Cyclooxygenase; Intercellular Adhesion Molecule-1 - analysis; Mice; Mice, Knockout; NADPH Oxidases - analysis; Prostaglandin E1; Vascular Cell Adhesion Molecule-1 - analysis; Vasodilation
• ISSN: 1340-3478; 1880-3873
• DOI: 10.5551/jat.No430

Aim: Dihomo-γ-linolenic acid (DGLA) is an n-6 polyunsaturated fatty acid that is mainly metabolized to an anti-inflammatory eicosanoid, prostaglandin (PG) E1, via the cyclooxygenase (COX) pathway. We evaluated the effect of DGLA on atherosclerosis in apoE-deficient mice and studied the mechanism of the anti-atherosclerotic effect. Methods: ApoE-deficient mice were fed a normal diet supplemented with 0.5% DGLA or vehicle for 6 months. ApoE-deficient mice were also fed a high-cholesterol diet supplemented with 0.5% DGLA or vehicle for 1 month. To clarify the influence of a COX inhibitor, naproxen, on the anti-atherosclerotic effect of DGLA, age-matched apoE-deficient mice fed a high-cholesterol diet supplemented with 0.5% DGLA were given oral naproxen for 1 month. Results: In normal diet-fed mice, acetylcholine-induced vascular relaxation was significantly greater in the DGLA group than in the vehicle group. NADPH oxidase subunits, p22phox and gp91phox, intercellular adhesion molecule-1, and vascular cellular adhesion molecule-1 were significantly lower in the DGLA group than in the vehicle group, and DGLA significantly prevented atherosclerosis. In high-cholesterol diet-fed mice, DGLA also significantly prevented atherosclerosis, but the anti-atherosclerotic effect was attenuated by naproxen. Conclusion: DGLA may have an anti-atherosclerotic effect in apoE-deficient mice via PGE1 formation.