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Articles

Dietary -Linolenic Acid Suppresses Aortic Smooth Muscle Cell Proliferation and Modifies Atherosclerotic Lesions in Apolipoprotein E Knockout Mice¹

Yang-Yi Fan^*, Kenneth S. Ramos^,** and Robert S. Chapkin^*,2

^* Molecular and Cell Biology Section, Faculty of Nutrition, Center for Environmental and Rural Health and ^** Department of Veterinary Physiology and Pharmacology, Texas A&M University, College Station, Texas 77840

²To whom correspondence should be addressed at 442 Kleberg Biotechnology Center, 2471 TAMU, Texas A & M University, College Station, TX 77843-2471. E-mail: r-chapkin{at}tamu.edu

The present study was conducted to evaluate the antiatherogenic effects of dietary -linolenic acid (GLA) (primrose oil) in apolipoprotein E (apoE) genetic knockout mice. Five-wk-old male mice were fed cholesterol-free diets 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 mol GLA and 17 mol/100 mol (n-3) PUFA] or fish oil-PO mix [FP, 1:3 wt/wt, 8 mol/100 mol GLA and 5 mol/100 mol (n-3) PUFA] for 15 wk. Subsequently, diets were supplemented 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 levels 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 liver phospholipid levels of dihomo--linolenic acid, the elongated product of GLA, relative to CO and FC groups. Consumption of GLA (PO and FP diets) significantly reduced (P < 0.05) aortic vessel wall medial layer thickness 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 reduced (P < 0.05) atherosclerotic lesion size in 30-wk-old mice. These results indicate that dietary GLA can suppress smooth muscle cell proliferation in vivo and retard the development of diet-induced atherosclerosis in apoE knockout mice.

KEY WORDS: • gamma-linolenic acid • fish oil • aortic smooth muscle cells • apoE knockout mouse • atherosclerosis.

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