TY - JOUR
T1 - A brief elevation of serum amyloid A is suffi cient to increase atherosclerosis
AU - Thompson, Joel C.
AU - Jayne, Colton
AU - Thompson, Jennifer
AU - Wilson, Patricia G.
AU - Yoder, Meghan H.
AU - Webb, Nancy
AU - Tannock, Lisa R.
PY - 2015/2/1
Y1 - 2015/2/1
N2 - Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-defi cient ( rag1 ) × apolipoprotein E-defi cient ( apoe ) and apoe male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefl y elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-) signaling prevents SAA-induced increases in LDL retention and SAAinduced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term infl ammation with concomitant increase in SAA may increase the risk of developing CVD.
AB - Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-defi cient ( rag1 ) × apolipoprotein E-defi cient ( apoe ) and apoe male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefl y elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-) signaling prevents SAA-induced increases in LDL retention and SAAinduced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term infl ammation with concomitant increase in SAA may increase the risk of developing CVD.
KW - Apolipoproteins
KW - Cardiovascular Disease
KW - Extracellular Matrix
KW - Free-Form: Biglycan
KW - Lipoproteins
KW - Proteoglycans
KW - Transforming Growth Factor Beta
KW - Vascular Biology
UR - http://www.scopus.com/inward/record.url?scp=84921951426&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84921951426&partnerID=8YFLogxK
U2 - 10.1194/jlr.M054015
DO - 10.1194/jlr.M054015
M3 - Article
C2 - 25429103
AN - SCOPUS:84921951426
SN - 0022-2275
VL - 56
SP - 286
EP - 293
JO - Journal of Lipid Research
JF - Journal of Lipid Research
IS - 2
ER -