Adenoviral overexpression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice.
Mice lacking ApoA-V, a novel HDL-associated apolipoprotein identified by our group and independently by Pennacchio et al. [Science 294 (2001) 169], were recently shown to be hypertriglyceridemic. To study the role of ApoA-V in triglyceride homeostasis, we compared lipid profiles in mice expressing normal and highly elevated levels of ApoA-V. For this purpose, adenoviral vectors expressing sense or antisense ApoA-V cDNA were constructed. Treatment of mice with sense adenoviral constructs resulted in circa 20-fold higher serum ApoA-V levels compared with mice injected with either PBS or antisense adenoviral constructs. ApoA-V overexpressing mice had markedly decreased (-70%) serum triglyceride levels caused primarily by lowered triglyceride content of the VLDL fraction. Furthermore, in these mice cholesterol levels were found to be lowered in all lipoprotein fractions with the largest mass decrease in the HDL fraction. This resulted in a 40% drop of serum cholesterol content. These findings suggest a role of ApoA-V in regulating levels of circulating triglycerides and cholesterol.
AMC Liver Center, Meibergdreef 69-71, 1105 BK Amsterdam, the Netherlands.
Hendrik N
HN
van der Vliet
Frank G
FG
Schaap
Johannes H M
JH
Levels
Roelof
R
Ottenhoff
Norbert
N
Looije
John G
JG
Wesseling
Albert K
AK
Groen
Robert A F M
RA
Chamuleau
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002784:Cholesterol / Q000097:blood*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006706:Homeostasis / Q000502:physiology*; D008297:Male; D051379:Mice; D023421:Models, Animal; D014280:Triglycerides / Q000097:blood*
C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D014280:Triglycerides; D002784:Cholesterol