Serum Amyloid A and Lipoprotein Retention in Murine Models of Atherosclerosis

O’Brien, Kevin D.; McDonald, Thomas O.; Kunjathoor, Vidya V.; Eng, KimLi; Knopp, Eleanor A.; Lewis, Katherine E.; Lopez, Roland; Kirk, Elizabeth A.; Chait, Alan; Wight, Thomas N.; Debeer, F. C.; LeBoeuf, Renée C.

doi:10.1161/01.atv.0000158383.65277.2b

Cited by 102 publications

(97 citation statements)

References 45 publications

(54 reference statements)

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“…For IHC, ATs were fixed in 10% formalin for immunohistochemical staining with apoA-I (Rockland Immunochemicals, 600-101-196, 1:4000) or SAA (R&D Systems, AF2948, 1:25) antibodies, as described previously (86). Images were morphometrically analyzed using Image Pro Plus 6.0 (Media Cybernetics).…”

Section: Methodsmentioning

confidence: 99%

Serum amyloid A impairs the antiinflammatory properties of HDL

Han¹,

Tang²,

Guevara³

et al. 2015

Journal of Clinical Investigation

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131

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Section: Methodsmentioning

confidence: 99%

Serum amyloid A impairs the antiinflammatory properties of HDL

Han¹,

Tang²,

Guevara³

et al. 2015

Journal of Clinical Investigation

Self Cite

131

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“…Previous reports suggest that an acute phase response is closely associated with lipoprotein abnormalities and that SAA, which is mainly associated with plasma HDL, is involved in the development of atherosclerosis (40,41). In fact, SAA expression has been reported in human atherosclerotic lesions (41), and it has been suggested that SAA is involved in lipoprotein retention in atherosclerosis (42). It has also been demonstrated that oxidized low density lipoprotein induces acute phase SAA, thus suggesting that SAA participates in vascular injury and atherosclerosis (43).…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A Induces CCL2 Production via Formyl Peptide Receptor-Like 1-Mediated Signaling in Human Monocytes

Lee

Kim

Shim

et al. 2008

The Journal of Immunology

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Although the presence of an elevated level of serum amyloid A (SAA) has been regarded as a cardiovascular risk factor, the role of SAA on the progress of atherosclerosis has not been fully elucidated. In the present study, we investigated the effect of SAA on the production of CCL2, an important mediator of monocyte recruitment, and the mechanism underlying the action of SAA in human monocytes. The stimulation of human monocytes with SAA elicited CCL2 production in a concentration-dependent manner. The production of CCL2 by SAA was found to be mediated by the activation of NF-κB. Moreover, the signaling events induced by SAA included the activation of ERK and the induction of cyclooxygenase-2, which were required for the production of CCL2. Moreover, SAA-induced CCL2 induction was inhibited by a formyl peptide receptor-like 1 (FPRL1) antagonist. We also found that the stimulation of FPRL1-expressing RBL-2H3 cells induced CCL2 mRNA accumulation, but the vector-expressing RBL-2H3 cells combined with SAA did not. Taken together, our findings suggest that SAA stimulates CCL2 production and, thus, contributes to atherosclerosis. Moreover, FPRL1 was found to be engaged in SAA-induced CCL2 induction, and cyclooxygenase-2 induction was found to be essential for SAA-induced CCL2 expression. These results suggest that SAA and FPRL1 offer a developmental starting point for the treatment of atherosclerosis.

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“…15,61 Additionally, SAA has been shown to be synthesized by all cell types pertinent to atherosclerosis, including vascular smooth muscle cells, endothelial cells, and macrophages. 18 The co-localization of SAA with biglycan observed in our studies could be attributable to production or deposition of SAA in the vascular wall where it directly stimulates vascular smooth muscle cell biglycan synthesis, or could be attributable to biglycan-mediated retention of SAA-containing lipoproteins.…”

Section: Discussionmentioning

confidence: 99%

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

Wilson

Thompson

Webb

et al. 2008

The American Journal of Pathology

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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 (K d , 29 g/ml LDL versus 90 g/ml LDL for SAA versus control proteoglycans; P < 0.005). Furthermore, SAA up-regulated biglycan via the induction of endogenous transforming growth factor (TGF)-␤. 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-␤ 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-␤ and may play a causal role in the development of atherosclerosis.

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Serum Amyloid A and Lipoprotein Retention in Murine Models of Atherosclerosis

Cited by 102 publications

References 45 publications

Serum amyloid A impairs the antiinflammatory properties of HDL

Serum amyloid A impairs the antiinflammatory properties of HDL

Serum Amyloid A Induces CCL2 Production via Formyl Peptide Receptor-Like 1-Mediated Signaling in Human Monocytes

Serum Amyloid A, but Not C-Reactive Protein, Stimulates Vascular Proteoglycan Synthesis in a Pro-Atherogenic Manner

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