Apolipoprotein A-II: beyond genetic associations with lipid disorders and insulin resistance.
OBJECTIVE
Apolipoprotein A-II, the second major HDL apolipoprotein, was often considered of minor importance relatively to apolipoprotein A-I and its role was controversial. This picture is now rapidly changing, due to novel polymorphisms and mutations, to the outcome of clinical trials, and to studies with transgenic mice.


RESULTS
The -265 T/C polymorphism supports a role for apolipoprotein A-II in postprandial very-low-density lipoprotein metabolism. Fibrates, which increase apolipoprotein A-II synthesis, significantly decrease the incidence of major coronary artery disease events, particularly in subjects with low HDL cholesterol, high plasma triglyceride, and high body weight. The comparison of transgenic mice overexpressing human or murine apolipoprotein A-II has highlighted major structural differences between the two proteins; they have opposite effects on HDL size, apolipoprotein A-I content, plasma concentration, and protection from oxidation. Human apolipoprotein A-II is more hydrophobic, displaces apolipoprotein A-I from HDL, accelerates apolipoprotein A-I catabolism, and its plasma concentration is decreased by fasting. Apolipoprotein A-II stimulates ATP binding cassette transporter 1-mediated cholesterol efflux. Human and murine apolipoprotein A-II differently affect glucose metabolism and insulin resistance. A novel beneficial role for apolipoprotein A-II in the pathogenesis of hepatitis C virus has been shown.


CONCLUSIONS
The hydrophobicity of human apolipoprotein A-II is a key regulatory factor of HDL metabolism. Due to the lower plasma apolipoprotein A-II concentration during fasting, measurements of apolipoprotein A-II in fed subjects are more relevant. More clinical studies are necessary to clarify the role of apolipoprotein A-II in well-characterized subsets of patients and in the insulin resistance syndrome.
Kalopissis
Athina-Despina
AD
Unité 505 INSERM, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006 Paris, France. athina.kalopissis-u505@bhdc.jussieu.fr
Pastier
Danièle
D
Chambaz
Jean
J
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016633:Apolipoprotein A-II / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism
D000975:Antioxidants; D016633:Apolipoprotein A-II; D002784:Cholesterol; D005947:Glucose