Suppression of induced atherosclerosis in h-apo AI transgenic mice by overexpression of human apo AI in the aortic wall

Objectives To investigate the inhibitory effect of expressed human apolipop rotein Al (h-apo Al) and high density lipoprotein (HDL) on atherosclerosis development in transgenic mice, and cultivation of smooth muscle cells isol ated from the aortic wall of transgenic mice that are able to produce human apo Al in vitro. Methods Both h-apo Al transgenic mice and normal C57 mice were fed with eit her a regular chow or a high-fat diet containing 5% pork lard, 1.25% choles terol and 0.25% sodium cholate for 14 or 24 weeks respectively. Human apo A l mRNA were detected by Northern blot. Plasma apo Al levels were measured u sing a radio-immuno-diffusion assay, and plasma lipid levels were measured using a colorimetric assay. Image analysis was performed in order to quanti fy the fatty streak areas stained with oil red O. In addition, smooth muscl e cells isolated from the media layer of the aortic wall of h-apo Al transg enic mice were cultured for the detection of human apo Al produced. Results Higher levels of h-apo Al mRNA were found in liver, small intestine , kidneys and aortae in transgenic mice than in the controls all on a high- fat diet. The transgenic mice had an increased level of serum apo Al and HD L-cholesterol and the far,streak area counted at the aortic sinus was appro ximately 5-fold less in the transgenic mice after feeding with a high fat r ation, particularly after 24 weeks, SMC isolated from the transgenic mice a ortae were cultivated and able to express h-apo Al mRNA and its related pro tein. Conclusion Elevation of h-apo Al and HDL in serum and aortic wall of the tr ansgenic mice has a remarkably inhibitory effect on the development of expe rimental atherosclerosis.