Role of apoA-II in lipid metabolism and atherosclerosis: advances in the study of an enigmatic protein.

Abstract

Our understanding of apolipoprotein A-II (apoA-II) physiology is much more limited than that of apoA-I. However, important and rather surprising advances have been produced, mainly through analysis of genetically modified mice. These results reveal a positive association of apoA-II with FFA and VLDL triglyceride plasma concentrations; however, whether this is due to increased VLDL synthesis or to decreased VLDL catabolism remains a matter of controversy. As apoA-II-deficient mice present a phenotype of insulin hypersensitivity, a function of apoA-II in regulating FFA metabolism seems likely. Studies of human beings have shown the apoA-II locus to be a determinant of FFA plasma levels, and several genome-wide searches of different populations with type 2 diabetes have found linkage to an apoA-II intragenic marker, making apoA-II an attractive candidate gene for this disease. The increased concentration of apoB-containing lipoproteins present in apoA-II transgenic mice explains, in part, why these animals present increased atherosclerosis susceptibility. In addition, apoA-II transgenic mice also present impairment of two major HDL antiatherogenic functions: reverse cholesterol transport and protection of LDL oxidative modification. The apoA-II locus has also been suggested as an important genetic determinant of HDL cholesterol concentration, even though there is a major species-specific difference between the effects of mouse and human apoA-II. As antagonizing apoA-I antiatherogenic actions can hardly be considered the apoA-II function in HDL, this remains a topic for future investigations. We suggest that the existence of apoA-II or apoA-I in HDL could be an important signal for specific interaction with HDL receptors such as cubilin or heat shock protein 60.

• Authors: F Blanco-Vaca, J C Escolà-Gil, J M Martín-Campos, J Julve
• Journal: Journal of lipid research (J Lipid Res) Vol. 42 Issue 11 Pg. 1727-39 (Nov 2001) ISSN: 0022-2275 [Print] United States
• PMID: 11714842 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Apolipoprotein A-II
• Apolipoproteins B
• Cholesterol, HDL
• Fatty Acids, Nonesterified
• Lipoproteins, VLDL
• Triglycerides
• Cholesterol

Topics

• Animals
• Apolipoprotein A-II (chemistry, deficiency, genetics, physiology)
• Apolipoproteins B (blood)
• Arteriosclerosis (genetics)
• Biological Transport
• Cholesterol (metabolism)
• Cholesterol, HDL (blood)
• Fatty Acids, Nonesterified (blood)
• Gene Expression Regulation
• Genetic Predisposition to Disease
• Humans
• Lipid Metabolism
• Lipid Peroxidation
• Lipoproteins, VLDL (blood)
• Mice
• Mice, Transgenic
• Triglycerides (blood)