Serum Amyloid P Component Associates with High Density Lipoprotein as well as Very Low Density Lipoprotein but Not with Low Density Lipoprotein

doi:10.1006/bbrc.1998.8248

Biochemical and Biophysical Research Communications

Volume 244, Issue 1, 6 March 1998, Pages 249-252

https://doi.org/10.1006/bbrc.1998.8248 Get rights and content

Abstract

Serum amyloid P component (SAP) is a glycoprotein in human plasma. We previously showed that SAP is specifically localized in human atherosclerotic lesions, suggesting that SAP may play a role in atherogenesis. In this study, the interactions between human SAP and high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) were investigated by using a solid phase plate assay. Biotinylated SAP bound to immobilized HDL and VLDL in a calcium-dependent, saturable manner. The SAP–HDL and SAP–VLDL bindings reached saturation at 4 nM and 16 nM of SAP, respectively. The bindings were inhibited by native SAP in a dose-dependent manner. No binding between SAP and LDL was found in the presence of calcium or EDTA, which indicates the specificity of SAP–lipoproteins interactions. These results suggest that the function of SAP is related to its capability to interact with lipoproteins and this may have important implications in atherosclerosis and in amyloidosis.

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The immune system is divided into two broad categories, consisting of innate and adaptive immunity. As recognition and effector factors of innate immunity and regulators of adaptive immune responses, lectins are considered to be important defense chemicals against microbial pathogens, cell trafficking, immune regulation, and prevention of autoimmunity. Pentraxins, important members of animal lectins, play a significant role in protecting the body from pathogen infection and regulating inflammatory reactions. They can recognize and bind to a variety of ligands, including carbohydrates, lipids, proteins, nucleic acids and their complexes, and protect the host from pathogen invasion by activating the complement cascade and Fcγ receptor pathways. Based on the primary structure of the subunit, pentraxins are divided into short and long pentraxins. The short pentraxins are comprised of C-reactive protein (CRP) and serum amyloid P (SAP), and the most important member of the long pentraxins is pentraxin 3 (PTX3). The CRP and SAP exist in both vertebrates and invertebrates, while the PTX3 may be present only in vertebrates. The major ligands and functions of CRP, SAP and PTX3 and three activation pathways involved in the complement system are summarized in this review. Their different characteristics in various animals including humans, and their evolutionary trees are analyzed. The clinical applications of CRP, SAP and PTX3 in human are reviewed. Some questions that remain to be understood are also highlighted.
The pentraxin family in autoimmune disease
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The pentraxins represent a family of multifunctional proteins composed of long and short pentamers. The latter includes serum amyloid P component (SAP) and C-reactive protein (CRP) whereas the former includes neuronal PTX1 and PTX2 (NPTX1 and NPTX2, respectively), PTX3 and PTX4. These serve as a bridge between adaptive immunity and innate immunity and a link between inflammation and immunity. Similarities and differences between long and short pentamers are examined and their roles in autoimmune disease are discussed. Increased CRP and PTX3 could indicate the activity of rheumatoid arthritis, systemic lupus erythematosus or other autoimmune diseases. Mechanistically, CRP and PTX3 may predict target organ injury, regulate bone metabolic immunity and maintain homeostasis as well as participate in vascular endothelial remodeling. Interestingly, PTX3 is pleiotropic, being involved in inflammation and tissue repair. Given the therapeutic potential of PTX3 and CRP, targeting these factors to exert a beneficial effect is the focus of research efforts. Unfortunately, studies on NPTX1, NPTX2, PTX4 and SAP are scarce and more research is clearly needed to elaborate their potential roles in autoimmune disease.
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High-fat diet (HFD)–induced inflammation is associated with a variety of health risks. The systemic pentraxin serum amyloid P (SAP) inhibits inflammation. SAP activates the high-affinity IgG receptor Fcγ receptor I (FcγRI; CD64) and the lectin receptor dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin (DC-SIGN; CD209). Herein, we show that for mice on an HFD, injections of SAP and a synthetic CD209 ligand (1866) reduced HFD-increased adipose and liver tissue inflammation, adipocyte differentiation, and lipid accumulation in adipose tissue. HFD worsened glucose tolerance test results and caused increased adipocyte size; for mice on an HFD, SAP improved glucose tolerance test results and reduced adipocyte size. Mice on an HFD had elevated serum levels of IL-1β, IL-23, interferon (IFN)-β, IFN-γ, monocyte chemoattractant protein 1 [MCP-1; chemokine (C-C motif) ligand 2 (CCL2)], and tumor necrosis factor-α. SAP reduced serum levels of IL-23, IFN-β, MCP-1, and tumor necrosis factor-α, whereas 1866 reduced IFN-γ. In vitro, SAP, but not 1866, treated cells isolated from white fat tissue (stromal vesicular fraction) produced the anti-inflammatory cytokine IL-10. HFD causes steatosis, and both SAP and 1866 reduced it. Conversely, compared with control mice, SAP knockout mice fed on a normal diet had increased white adipocyte cell sizes, increased numbers of inflammatory cells in adipose and liver tissue, and steatosis; and these effects were exacerbated on an HFD. SAP and 1866 may inhibit some, but not all, of the effects of a high-fat diet.
Effect of Ambient Fine Particulate Matter Air Pollution and Colder Outdoor Temperatures on High-Density Lipoprotein Function
2018, American Journal of Cardiology
Citation Excerpt :
However, we found no evidence for increased MPO-specific (3-chlorotyrosine) or other oxidative changes (3-nitrotyrosine and o,o′-dityrosine) on HDL protein despite using a highly sensitive assay liquid chromatography-electrospray ionization tandem mass spectrometry. It is possible that HDL oxidation and/or modification could have arisen from other sources that went undetected—free metal ions and radicals, various enzymes, glucose, and acute phase reactants.26–29 In the current study, blunted CEC occurred in a delayed fashion—5 to 6 days after higher ambient PM2.5 levels but not acutely to 24-hour personal PM2.5 levels.
Fine particulate matter (PM_2.5) air pollution and environmental temperatures influence cardiovascular morbidity and mortality. Recent evidence suggests that several air pollutants can promote dyslipidemia; however, the impact of ambient PM_2.5 and temperature on high-density lipoprotein (HDL) function remains unclear. We hypothesized that daily exposures to higher levels of ambient PM_2.5 and colder outdoor temperatures would impair HDL functionality. Lipoproteins, serum cholesterol efflux capacity (CEC), and HDL oxidation markers were measured twice in 50 healthy adults (age 32.1 ± 9.6 years) living in southeast Michigan and associated with ambient and personal-level exposures using mixed models. Although previous 7-day mean outdoor temperature (4.4 ± 9.8°C) and PM_2.5 levels (9.1 ± 1.8 µg/m³) were low, higher ambient PM_2.5 exposures (per 10 µg/m³) were associated with significant increases in the total cholesterol-to-HDL-C ratio (rolling average lag days 1 and 2) as well as reductions in CEC by −1.93% (lag day 5, p = 0.022) and −1.62% (lag day 6, p = 0.032). Colder outdoor temperatures (per 10°C) were also associated with decreases in CEC from −0.62 to −0.63% (rolling average lag days 5 and 7, p = 0.027 and 0.028). Previous 24-hour personal-level PM_2.5 and temperature exposures did not impact outcomes, nor were any exposures associated with changes in HDL-oxidation metrics. In conclusion, we provide the first evidence that ambient PM_2.5 (even at low levels) and outdoor temperatures may influence serum CEC, a critical antiatherosclerotic HDL function.
SAP deficiency mitigated atherosclerotic lesions in ApoE<sup>-/-</sup> mice
2016, Atherosclerosis
Citation Excerpt :
Pro-inflammatory serum amyloid A(SAA) protein and CRP involved in HDL dysfunction. Likewise, although SAP could bind to HDL with high affinity [19], whether SAP promotes HDL dysfunction during the development of atherosclerosis needed to be confirmed. Besides, we only observed the effect of SAP deficiency on early stage of atherosclerosis at 4wk and 8wk after feeding western diet, in which both the deposition of oxidized lipids and the infiltration of macrophages are typically pathological features [55,56].
Serum amyloid P conpoent (SAP), a member of the pentraxin family, interact with pathogens and cell debris to promote their removal by macrophages and neutrophils and is co-localized with atherosclerotic plaques in patients. However, the exact mechanism of SAP in atherogenesis is still unclear. We investigated whether SAP influence macrophage recruitment and foam cell formation and ultimately affect atherosclerotic progression.
we generated apoE^−/−; SAP^−/− (DKO) mice and fed them western diet for 4 and 8 weeks to characterize atherosclerosis development.
SAP deficiency effectively reduced plaque size both in the aorta (p = 0.0006 for 4 wks; p = 0.0001 for 8 wks) and the aortic root (p = 0.0061 for 4 wks; p = 0.0079 for 8wks) compared with apoE^−/− mice. Meanwhile, SAP deficiency inhibited oxLDL-induced foam cell formation (p = 0.0004) compared with apoE^−/− mice and SAP treatment increases oxLDL-induced foam cell formation (p = 0.002) in RAW cells. Besides, SAP deficiency reduced macrophages recruitment (p = 0.035) in vivo and in vitro (p = 0.026). Furthermore, SAP treatment enhanced CD36 (p = 0.007) and FcγRI (p = 0.031) expression induced by oxLDL through upregulating JNK and p38 MAPK phosphorylation whereas specific JNK1/2 inhibitor reduced CD36 (p = 0.0005) and FcγRI (P = 0.0007) expression in RAW cell. SAP deficiency also significantly decreased the expression of M1 and M2 macrophage markers and inflammatory cytokines in oxLDL-induced macrophages.
SAP deficiency mitigated foam cell formation and atherosclerotic development in apoE^−/− mice, due to reduction in macrophages recruitment, polarization and pro-inflammatory cytokines and inhibition the CD36/FcγR-dependent signaling pathway.
SAP: Structure, function, and its roles in immune-related diseases
2015, International Journal of Cardiology
Citation Excerpt :
In 2007, Jenny and colleagues [23] hypothesized that SAP might be involved in a different aspect of inflammation and innate immunity in atherosclerosis, and these authors were the first to report the association between SAP and CHD outcomes. Other studies showed that SAP is present in atherosclerotic lesions and that SAP binds to high-density lipoprotein (HDL) and very low-density lipoprotein (VLDL) with high affinity, suggesting that SAP is involved in atherosclerosis and lipoprotein metabolism [24–26]. Recent studies further revealed that SAP co-localizes with apolipoprotein in human atheroma, and notably, plasma SAP levels are positively associated with cardiovascular disease in the elderly [23,27].
Serum amyloid P component (SAP), also known as pentraxin-2, is a member of the pentraxin protein family with an established relationship to the immune response. In the last century, SAP has been used as a diagnostic marker in amyloidosis diagnosis and patient follow-up. SAP has been thought to have potential for treating and curing amyloidosis and fibrosis diseases. More recently, it has been shown that SAP may serve as both a diagnostic marker and a therapeutic target for many immune-related diseases, such as cardiovascular, pulmonary, nephritic, neurological and autoimmune diseases. In the cardiovascular system, SAP has been defined as the culprit in amyloidosis in the heart. SAP may also exert a protective role during the early stage of atherosclerosis and myocardial fibrosis. In noncardiovascular system diseases, SAP is being developed for the treatment of pulmonary fibrosis. In this review, we summarize SAP history, structure, and its roles in immune-related diseases in different systems with emphasis on the cardiovascular system.

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^☆: This work was supported in part by National Natural Science Foundation of China, China Excellent Young Teacher's Foundation and Japan Cardiovascular Research Foundation.

^☆☆: The abbreviations used are: SAP, serum amyloid P component; CRP, C-reactive protein; HDL, high density lipoprotein; LDL, low density lipoprotein; VLDL, very low density lipoprotein; BSA, bovine serum albumin.

²: To whom correspondence should be addressed at National Cardiovascular Center Research Institute, 5-7-1 Fujishirodai, Suita, Osaka 565-8565, Japan. Fax: 81-6-872-7485; E-mail:[email protected].

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Regular ArticleSerum Amyloid P Component Associates with High Density Lipoprotein as well as Very Low Density Lipoprotein but Not with Low Density Lipoprotein☆,☆☆

Abstract

Methods Enzymol.

J. Biol. Chem.

J. Biol. Chem.

Biophys. Biochim. Acta

Biochem. Biophys. Res. Commun.

Biochim. Biophys. Acta

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

J. Biol. Chem.

Biochem. Biophys. Res. Commun.

Nature

Ann. N. Y. Acad. Sci.

Lab. Invest.

J. Exp. Med.

Nature

J. Exp. Med.

J. Exp. Med.

Regular Article
Serum Amyloid P Component Associates with High Density Lipoprotein as well as Very Low Density Lipoprotein but Not with Low Density Lipoprotein☆,☆☆