Journal
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
Volume 25, Issue 4, Pages 785-790Publisher
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000158383.65277.2b
Keywords
atherosclerosis; lipoproteins; perlecan; proteoglycans; serum amyloid A
Categories
Funding
- NHLBI NIH HHS [HL52848, HL02788, HL30086] Funding Source: Medline
Ask authors/readers for more resources
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 and Results - 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available