Dietary gamma-linolenic acid suppresses aortic smooth muscle cell proliferation and modifies atherosclerotic lesions in apolipoprotein E knockout mice

The present study was conducted to evaluate the antiatherogenic effects of dietary gamma -linolenic acid (GLA) (primrose oil) in apolipoprotein E (apo E) genetic knockout mice. Five-wk-old male mice were fed cholesterol-free d iets containing 10 g/100 g lipid as corn oil (CO) [control diet, 0 mol/100 mol GLA and (n-3) polyunsaturated fatty acids (PUFA)], primrose oil (PO, 10 mol/100 mol GLA), fish oil-CO mix [FC; 9:1 wt/wt, 0 mol/100 mot GLA and 17 mol/100 mol (n-3) PUFA] or fish oil-PO mix [FP, 1:3 wt/wt, 8 mol/100 mol G LA and 5 mol/100 mol (n-3) PUFA] for 15 wk. Subsequently, diets were supple mented with cholesterol (1.25 g/100 g) and sodium cholate (0.5 g/100 g) and fed for an additional 10 and 16 wk. Plasma cholesterol and triglyceride le vels generally did not differ among groups at 20, 30 and 36 wk of age. Mice fed GLA-containing diets (PO and FP) had significantly (P < 0.05) higher l iver phospholipid levels of dihomo-gamma -linolenic acid, the elongated pro duct of GLA, relative to CO and FC groups. Consumption of GLA (PO and FP di ets) significantly reduced (P < 0.05) aortic vessel wall medial layer thick ness at 20 and 30 wk. A parallel GLA-dependent suppression in the number of proliferating (proliferating cell nuclear antigen positive) aortic smooth muscle cells was also observed. Diets containing either GLA or (n-3) PUFA r educed (p < 0.05) atherosclerotic lesion size in 30-wk-old mice. These resu lts indicate that dietary GLA can suppress smooth muscle cell proliferation in vivo and retard the development of diet-induced atherosclerosis in apoE knockout mice.