Serum amyloid A, but not C-reactive protein, stimulates vascular proteoglycan synthesis in a pro-atherogenic manner

Patricia G. Wilson, Joel C. Thompson, Nancy R. Webb, Frederick C. De Beer, Victoria L. King, Lisa R. Tannock

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57 Scopus citations

Abstract

Inflammatory markers serum amyloid A (SAA) and C-reactive protein (CRP) are predictive of cardiac disease and are proposed to play causal roles in the development of atherosclerosis, in which the retention of lipoproteins by vascular wall proteoglycans is critical. The purpose of this study was to determine whether SAA and/or CRP alters vascular proteoglycan synthesis and lipoprotein retention in a pro-atherogenic manner. Vascular smooth muscle cells were stimulated with either SAA or CRP (1 to 100 mg/L) and proteoglycans were then isolated and characterized. SAA, but not CRP, increased proteoglycan sulfate incorporation by 50 to 100% in a dose-dependent manner (P < 0.0001), increased glycosaminoglycan chain length, and increased low-density lipoprotein (LDL) binding affinity (Kd, 29 μg/ml LDL versus 90 μg/ml LDL for SAA versus control proteoglycans; P < 0.005). Furthermore, SAA up-regulated biglycan via the induction of endogenous transforming growth factor (TGF)-β. To determine whether SAA stimulated proteoglycan synthesis in vivo, ApoE-/- mice were injected with an adenovirus expressing human SAA-1, a null virus, or saline. Mice that received adenovirus expressing SAA had increased TGF-β concentrations in plasma and increased aortic biglycan content compared with mice that received either null virus or saline. Thus, SAA alters vascular proteoglycans in a pro-atherogenic manner via the stimulation of TGF-β and may play a causal role in the development of atherosclerosis.

Original languageEnglish
Pages (from-to)1902-1910
Number of pages9
JournalAmerican Journal of Pathology
Volume173
Issue number6
DOIs
StatePublished - Dec 2008

Bibliographical note

Funding Information:
Supported in part by the National Institutes of Health (grants HL082772 to L.R.T. and HL086670 to N.R.W. and F.C.D. ), the American Heart Association (award to L.R.T.), and the University of Kentucky (the physician scientist program to L.R.T.).

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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