Inhibition of atherosclerotic lesion development in the ApoE-/- mouse by a novel β-oxa polyunsaturated fatty acid.

Recent findings that a novel polyunsaturated fatty acid, beta-oxa 23:4n-6, inhibits adhesion molecule expression on vascular endothelial cells and leukocyte adhesion led us to examine its ability to inhibit the development of atherosclerosis in the apoE-deficient (apoE(-/-)) mouse. The mice were kept on normal chow or a high-fat/high-cholesterol diet for various periods and treated with either vehicle or beta-oxa 23:4n-6 by the intraperitoneal route. The hearts and aortae were isolated and lesion development at the aortic root was determined. Morphometric assessment revealed that lesion development was a function of compensatory aortic enlargement, suggesting that measurement of plaque size per se is the appropriate assessment of lesion size. Using this criterion, we found that atherosclerosis development was reduced in response to beta-oxa 23:4n-6, plaque size by 74% and aortic cross-sectional area by 62%, under an optimized regime. The number of foam cells per unit tissue area in the lesions of beta-oxa 23:4n-6-treated mice was significantly reduced by 37.5%. The blood levels of beta-oxa23:4n-6 in these mice exceeded the concentrations previously found to inhibit adhesion molecule expression in cultured endothelial cells. These data show that beta-oxa23:4n-6 protects against experimental atherosclerosis, most likely by reducing the number of infiltrating monocytes.