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

Abstract

OBJECTIVES:

To investigate the inhibitory effect of expressed human apolipoprotein AI (h-apo AI) and high density lipoprotein (HDL) on atherosclerosis development in transgenic mice, and cultivation of smooth muscle cells isolated from the aortic wall of transgenic mice that are able to produce human apo AI in vitro.

METHODS:

Both h-apo AI transgenic mice and normal C57 mice were fed with either a regular chow or a high-fat diet containing 5% pork lard, 1.25% cholesterol and 0.25% sodium cholate for 14 or 24 weeks respectively. Human apo AI mRNA were detected by Northern blot. Plasma apo AI levels were measured using a radio-immuno-diffusion assay, and plasma lipid levels were measured using a colorimetric assay. Image analysis was performed in order to quantify the fatty streak areas stained with oil red O. In addition, smooth muscle cells isolated from the media layer of the aortic wall of h-apo AI transgenic mice were cultured for the detection of human apo AI produced.

RESULTS:

Higher levels of h-apo AI 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 AI and HDL-cholesterol and the fatty streak area counted at the aortic sinus was approximately 5-fold less in the transgenic mice after feeding with a high fat ration, particularly after 24 weeks. SMC isolated from the transgenic mice aortae were cultivated and able to express h-apo AI mRNA and its related protein.

CONCLUSION:

Elevation of h-apo AI and HDL in serum and aortic wall of the transgenic mice has a remarkably inhibitory effect on the development of experimental atherosclerosis.

• Authors: H Li, S Gu, X Cao, Z Wang, M She
• Journal: Chinese medical journal (Chin Med J (Engl)) Vol. 113 Issue 7 Pg. 657-61 (Jul 2000) ISSN: 0366-6999 [Print] China
• PMID: 11776042 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoprotein A-I
• Cholesterol, HDL
• RNA, Messenger

Topics

• Animals
• Aorta (metabolism)
• Apolipoprotein A-I (biosynthesis, blood, genetics)
• Arteriosclerosis (etiology)
• Cholesterol, HDL (blood)
• Female
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Transgenic
• Muscle, Smooth, Vascular (metabolism)
• RNA, Messenger (analysis)