Anti-atherosclerotic effects of dihomo-gamma-linolenic acid in ApoE-deficient mice.
OBJECTIVE
Dihomo-gamma-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.


CONCLUSIONS
DGLA may have an anti-atherosclerotic effect in apoE-deficient mice via PGE1 formation.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College,Takatsuki, Japan. pha010@art.osaka-med.ac.jp
Jin
Denan
D
Kawashima
Hiroshi
H
Kimura
Maki
M
Shiraishi-Tateishi
Akiko
A
Tanaka
Takao
T
Kakutani
Saki
S
Tanaka
Kazuhiko
K
Kiso
Yoshinobu
Y
Miyazaki
Mizuo
M
D015126:8,11,14-Eicosatrienoic Acid / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000527:Alprostadil / Q000096:biosynthesis; D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000188:drug therapy* / Q000517:prevention & control; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D051379:Mice; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000032:analysis; D019010:Vascular Cell Adhesion Molecule-1 / Q000032:analysis; D014664:Vasodilation
D001057:Apolipoproteins E; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D019255:NADPH Oxidases; D000527:Alprostadil; D015126:8,11,14-Eicosatrienoic Acid