Serum amyloid A and lipoprotein retention in murine models of atherosclerosis.
Arterioscler Thromb Vasc Biol
; 25(4): 785-90, 2005 Apr.
Article
in En
| MEDLINE
| ID: mdl-15692094
ABSTRACT
OBJECTIVE:
Elevated serum amyloid A (SAA) levels are associated with increased cardiovascular risk in humans. Because SAA associates primarily with lipoproteins in plasma and has proteoglycan binding domains, we postulated that SAA might mediate lipoprotein retention on atherosclerotic extracellular matrix. METHODS ANDRESULTS:
Immunohistochemistry was performed for SAA, apolipoprotein A-I (apoA-I), apolipoprotein B (apoB), and perlecan on proximal aortic lesions from chow-fed low-density lipoprotein receptor (LDLR)-/- and apoE-/- mice euthanized at 10, 50, and 70 weeks. SAA was detected on atherosclerotic lesion extracellular matrix at all time points in both strains. SAA area correlated highly with lesion areas (apoE-/-, r=0.76; LDLR-/-, r=0.86), apoA-I areas (apoE-/-, r=0.88; LDLR-/-, r=0.80), apoB areas (apoE-/-, r=0.74; LDLR-/-, r=0.89), and perlecan areas (apoE-/-, r=0.83; LDLR-/-, r=0.79) (all P<0.0001). In vitro, SAA enrichment increased high-density lipoprotein (HDL) binding to heparan sulfate proteoglycans, and immunoprecipitation experiments using plasma from apoE-/- and LDLR-/- mice demonstrated that SAA was present on both apoA-I-containing and apoB-containing lipoproteins.CONCLUSIONS:
In chow-fed apoE-/- and LDLR-/- mice, SAA is deposited in murine atherosclerosis at all stages of lesion development, and SAA immunoreactive area correlates highly with lesion area, apoA-I area, apoB area, and perlecan area. These findings are consistent with a possible role for SAA-mediated lipoprotein retention in atherosclerosis.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Apolipoproteins B
/
Arteriosclerosis
/
Serum Amyloid A Protein
/
Apolipoprotein A-I
Type of study:
Prognostic_studies
Limits:
Animals
Language:
En
Journal:
Arterioscler Thromb Vasc Biol
Journal subject:
ANGIOLOGIA
Year:
2005
Document type:
Article
Affiliation country: