Adenoviral vector-mediated overexpression of serum amyloid A in apoA-I-deficient mice.
Serum amyloid A (SAA) is an acute phase reactant that can become the predominant apolipoprotein of high density lipoprotein (HDL) during severe inflammatory states. However, the function of SAA is unknown. To study the ability of SAA to form HDL in the absence of apolipoprotein A-I, we expressed the mouse SAA pI 6.15 (CE/J) isoform in apolipoprotein A-I knock-out (apoA-I (-/-)) mice using a recombinant adenovirus. As a control, apoA-I (-/-) mice were injected with an adenovirus expressing human apoA-I. High level expression of plasma SAA was obtained in the absence of any endogenous acute phase SAA production. SAA expression increased plasma HDL cholesterol levels about 2-fold, but to a lesser extent than the expression of apoA-I (about 10-fold). The HDL particles isolated by density ultracentrifugation from SAA-expressing mice were heterogeneous in size and composition and rich in free cholesterol as well as apoE and apoA-IV. Of the SAA expressed in the plasma, only a small fraction (4%) was associated with HDL particles in contrast to expressed apoA-I, of which 62% was associated with HDL. We conclude that SAA is unable to substitute for apoA-I in HDL particle formation.
Webb
N R
NR
Department of Internal Medicine, University of Kentucky Medical Center, Lexington 40536, USA.
de Beer
M C
MC
van der Westhuyzen
D R
DR
Kindy
M S
MS
Banka
C L
CL
Tsukamoto
K
K
Rader
D L
DL
de Beer
F C
FC
D000210:Acute-Phase Reaction / Q000097:blood; D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016632:Apolipoprotein A-I / Q000172:deficiency* / Q000235:genetics; D001053:Apolipoproteins / Q000235:genetics* / Q000378:metabolism; D001054:Apolipoproteins A / Q000097:blood; D001057:Apolipoproteins E / Q000097:blood; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood / Q000737:chemistry; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000685:Serum Amyloid A Protein / Q000235:genetics* / Q000378:metabolism
D016632:Apolipoprotein A-I; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D000685:Serum Amyloid A Protein; C022205:apolipoprotein A-IV; D002784:Cholesterol