title: 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.affiliation: Servei de Bioquímica de l'Hospital de la Santa Creu i Sant Pau, Antoni M. Claret 167, 08025 Barcelona, Spain. fblancova@hsp.santpau.es
authors.forename: F
authors.initials: F
authors.lastname: Blanco-Vaca
authors.forename: J C
authors.initials: JC
authors.lastname: Escolà-Gil
authors.forename: J M
authors.initials: JM
authors.lastname: Martín-Campos
authors.forename: J
authors.initials: J
authors.lastname: Julve
mesh_terms: D000818:Animals; D016633:Apolipoprotein A-II / Q000737:chemistry / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D001055:Apolipoproteins B / Q000097:blood; D001161:Arteriosclerosis / Q000235:genetics*; D001692:Biological Transport; D002784:Cholesterol / Q000378:metabolism; D008076:Cholesterol, HDL / Q000097:blood; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005786:Gene Expression Regulation; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation; D008079:Lipoproteins, VLDL / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D014280:Triglycerides / Q000097:blood
chemical_list: D016633:Apolipoprotein A-II; D001055:Apolipoproteins B; D008076:Cholesterol, HDL; D005230:Fatty Acids, Nonesterified; D008079:Lipoproteins, VLDL; D014280:Triglycerides; D002784:Cholesterol