Protection Against Atherogenesis in Mice Mediated by Human Apolipoprotein A-IV

• Published in: Science (American Association for the Advancement of Science) Vol. 273; no. 5277; pp. 966 - 968
• Main Authors: Duverger, Nicolas, Tremp, Günter, Caillaud, Jean-Michel, Emmanuel, Florence, Castro, Graciela, Fruchart, Jean-Charles, Steinmetz, Armin, Denèfle, Patrice
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 16-08-1996; American Association for the Advancement of Science; The American Association for the Advancement of Science
• Subjects: Animals; Apolipoprotein A-I - blood; Apolipoproteins A - blood; Apolipoproteins A - physiology; Apolipoproteins E - blood; Apolipoproteins E - deficiency; Arteriosclerosis - prevention & control; Atherogenic diets; Atherosclerosis; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Cardiology. Vascular system; Cholesterol - blood; Cholesterol, HDL - blood; Cholesterols; Diet, Atherogenic; Female; HDL lipoproteins; High fat diet; Humans; Lesions; Lipids; Lipoproteins; Liver; Medical research; Medical sciences; Metabolism; Mice; Mice, Inbred C57BL; Mice, Transgenic; Proteins; Rodents; Transgenic animals; Human; Animal model; Rodentia; Transgenic animal; Cardiovascular disease; Gene expression; Vascular disease; Apolipoprotein A; Vertebrata; Phenotype; Mammalia; Gene; Mouse; Atherosclerosis; Risk factor; Predisposition; Genetics; Lipoprotein HDL
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.273.5277.966

Apollpoproteins are protein constituents of plasma lipid transport particles. Human apolipoprotein A-IV (apoA-IV) was expressed in the liver of C57BL/6 mice and mice deficient in apoE, both of which are prone to atherosclerosis, to investigate whether apoA-IV protects against this disease. In transgenic C57BL/6 mice on an atherogenic diet, the serum concentration of high density lipoprotein (HDL) cholesterol increased by 35 percent, whereas the concentration of endogenous apoA-I decreased by 29 percent, relative to those in transgenic mice on a normal diet. Expression of human apoA-IV in apoE-deficient mice on a normal diet resulted in an even more severe atherogenic lipoprotein profile, without affecting the concentration of HDL cholesterol, than that in nontransgenic apoE-deficient mice. However, transgenic mice of both backgrounds showed a substantial reduction in the size of atherosclerotic lesions. Thus, apoA-IV appears to protect against atherosclerosis by a mechanism that does not involve an increase in HDL cholesterol concentration.