Ms. Kindy et al., Expression of mouse acute-phase (SAA1.1) and constitutive (SAA4) serum amyloid A isotypes - Influence on lipoprotein profiles, ART THROM V, 20(6), 2000, pp. 1543-1550
The serum amyloid A (SAA) family of proteins consists of inducible acute-ph
ase members and a constitutive member that are minor apolipoproteins of nor
mal high density lipoprotein (HDL). During inflammation, HDL cholesterol an
d alaolipoprotein A-I (apoA-I) protein are decreased, and these changes are
thought to be partly related to the increase in acute-phase SAA proteins t
hat associate with the HDL particle to become the major apolipoprotein spec
ies. To determine the specific role of SAA. in the alteration of HDL in the
absence of a generalized acute-phase response, acute-phase Saa1.1 transgen
e expression was directed via an inducible mouse metallothionein promoter.
Elevated levels of SAA1.1 (28+/-9 mg/dL) comparable to a moderate acute-pha
se response were achieved over a 5-day period. SAA association with the HDL
particles at this concentration did not significantly alter the apoA-I or
HDL cholesterol levels or change the lipoprotein profiles in the transgenic
mice compared with wild-type mice, In addition, we used adenoviral vectors
to increase the SAA expression to levels seen in a major acute-phase respo
nse. Injection of adenovirus expressing the mouse SAA1.1 protein resulted i
n high-level expression (72+/-8 mg/dL) but did not alter apoA-I levels. How
ever, the SAA associated with the HDL particle gave rise to significantly l
arger HDL particles ( approximate to 10%). Adenoviral expression of the con
stitutive SAA4 protein resulted in an increase in HDL size (approximate to
10%) and an increase in very low density ligoprotein levels (20-fold) and t
riglyceride levels (1.7-fold), These studies suggest that increases in acut
e-phase SAA proteins alone are insufficient to alter HDL cholesterol or apo
A-I levels during inflammation. A role for constitutive SAA4 in HDL-very lo
w density lipoprotein interactions should be considered.