Characterization and change of phospholipids in the aorta of Watanabe hereditable hyperlipidemic rabbit.

Abstract

The characterization and change of lipids in aorta with the progression of atherosclerosis were elucidated in Watanabe hereditable hyperlipidemic (WHHL) rabbit, an animal model for human familial hypercholesterolemia as compared with those of normal rabbits. The amount of total phospholipids in the aorta of WHHL rabbit increased about 6-fold that of normal level. Sphingomyelin showed the largest increase and phosphatidylcholine the second in the aorta of WHHL rabbit. The fatty acid composition of sphingomyelin was characteristic of higher content of unsaturated fatty acids. It was suggested that the specific increase in both sphingomyelin and its unsaturated fatty acid content might be ascribed to regulation mechanism to recover the membrane fluidity which was reduced by the marked accumulation of cholesterol in the aorta of WHHL rabbit. Glycerophospholipids in the aorta of WHHL rabbit also contained more unsaturated fatty acids than those in normal ones. It was suggested that the higher amounts of unsaturated fatty acids of glycerophospholipids might be derived from those of serum lipoproteins and that they also might help to restore or recover membrane fluidity in the cholesterol-accumulated aorta of WHHL rabbit. Phosphatidylcholine in the aorta of WHHL rabbit contained a large amount of alkylacyl type-homologue (25-fold normal level) which was a precursor of platelet-activating factor (PAF). The increase of lysophosphatidylcholine, a potent chemotactic factor for monocyte, was also observed in WHHL rabbit. The increase of these chemical mediators indicated severe pathologic state in the atherosclerotic lesions of the aorta of WHHL rabbit.