REDUCED AORTIC LESIONS AND ELEVATED HIGH-DENSITY-LIPOPROTEIN LEVELS IN TRANSGENIC MICE OVEREXPRESSING MOUSE APOLIPOPROTEIN A-IV

Transgenic mouse lines carrying several copies of the mouse apo A-IV g ene were produced. Lipoprotein composition and function, and aortic le sion development were examined. Apo A-IV levels in the plasma of trans genic mice were elevated threefold compared with nontransgenic litterm ates on a chow diet, and sixfold in mice fed an atherogenic diet. Plas ma concentrations of total cholesterol, HDL cholesterol, triglycerides , and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0. 05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and f ree fatty acids (P < 0.05), and lower levels of unesterified cholester ol (P < 0.05), than nontransgenic littermates. Expression of the apo A -IV transgene had a protective effect against the formation of diet-in duced aortic lesions, with transgenics exhibiting lesion scores of sim ilar to 30% those seen in control mice. HDL-sized lipoproteins isolate d from transgenic mice fed the atherogenic diet promoted cholesterol e fflux from cholesterol-loaded human monocytes more efficiently than co mparable lipoproteins from nontransgenic counterparts. Plasma from tra nsgenics also exhibited higher endogenous cholesterol esterification r ates. Taken together, these results suggest that apo A-IV levels influ ence the metabolism and antiatherogenic properties of HDL.