Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Rowe, I. F.; Soutar, Anne K.; Trayner, I.; Baltz, M L; Beer, Frederick C. de; Walker, Louise N.; Bowyer, David E.; Herbert, Jeff; Feinstein, A.; Pepys, Mark B.

doi:10.1084/jem.159.2.604

Cited by 31 publications

(20 citation statements)

References 21 publications

(20 reference statements)

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“…The discrepancy between our study and a previous study is clearly due to the extreme differences in blood cholesterol levels of the subjects. It has been reported that CRP can selectively bind to apoB-containing atherogenic lipoproteins; such as VLDL and LDL, in hypercholesterolemic rabbits as well as in humans, 34 thus increased levels of LDL-C may facilitate the formation of CRP-lipoprotein complexes in circulation. Furthermore, hypercholesterolemia may induce systemic inflammatory response through overproduction of oxidized LDL.…”

Section: Discussionmentioning

confidence: 99%

Effects of Atorvastatin on C-reactive Protein Secretions by Adipocytes in Hypercholesterolemic Rabbits

Zhang¹,

Che²,

Zhao³

et al. 2007

Journal of Cardiovascular Pharmacology

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C-reactive protein (CRP) is a powerful predictor for coronary heart diseases. Recent study has revealed that adipocytes can produce CRP. Peroxisome proliferator-activated receptor (PPAR) gamma, an important nuclear transcriptional factor, can be predominately detected in adipocytes and exert several biological properties, including antiinflammatory effects. The authors investigated the effects of 2-week atorvastatin treatment on CRP secretions by adipocytes in hypercholesterolemic rabbits. CRP concentrations in serum and adipocytes culture supernatants were measured by latex particle-enhanced immunoturbidometric method. RT-PCR was used to evaluate PPARgamma mRNA expression. Two weeks of atorvastatin treatment resulted in significant reductions of circulating CRP concentrations, which were associated with CRP secretions in adipocytes (r = 0.688, P = 0.007). Meanwhile, CRP secretions in adipocytes were intimately related to low-density lipoprotein (LDL) cholesterol levels (r = 0.869, P < 0.001) and PPARgamma mRNA expressions in adipocytes (r = -0.857, P < 0.001). These data demonstrate that hypercholesterolemia may induce CRP secretions in adipocytes; short-term atorvastatin treatment reduces CRP secretions in adipocytes, possibly through lowering blood cholesterol levels and upregulating PPARgamma expressions in adipocytes. These findings enrich the pharmacological effects of statins and also enlighten the relationship between adipocytes and hypercholesterolemia.

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Section: Discussionmentioning

confidence: 99%

Effects of Atorvastatin on C-reactive Protein Secretions by Adipocytes in Hypercholesterolemic Rabbits

Zhang¹,

Che²,

Zhao³

et al. 2007

Journal of Cardiovascular Pharmacology

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“…Therefore, we also studied activation of complement by native CRP interacting with ligands in rat plasma. The CRP baseline level in rats is about 0·5 g/l 8,30–32 . Hence, we studied activation of complement via CRP by incubating NRP with different CRP ligands, without additional CRP supplementation.…”

Section: Discussionmentioning

confidence: 99%

Rat C‐reactive protein activates the autologous complement system

et al. 2003

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Activation of complement is a biological function of human C-reactive protein (hCRP), whereas rat CRP (rCRP) has been claimed to be unable to activate complement. As important biological functions of proteins are probably conserved among species, we re-evaluated, using various ligands, the capability of rCRP to activate complement. The activation of complement by hCRP and rCRP was investigated in solid- and fluid-phase systems. In the solid-phase system, purified CRP was fixed to enzyme-linked immunosorbent assay (ELISA) plates and incubated with human or rat recalcified plasma. Dose-dependent binding of human and rat C3 and C4 was observed to human and rat CRP, respectively. In the fluid-phase system, recalcified rat plasma, which contains about 500 mg/l of CRP, or human plasma supplemented with hCRP, were incubated with lyso-phosphatidylcholine. A dose-dependent activation of complement was observed upon incubation with this ligand, as reflected by the generation of activated C4 as well as of CRP-complement complexes. This activation was, in both cases, inhibited by preincubation of plasma with p-aminophosphorylcholine, a specific inhibitor of the interaction of CRP with its ligands, or by chelation of calcium ions. We conclude that rat CRP, similarly to human CRP, can activate autologous complement. These results support the notion that opsonization of ligands with complement is an important biological function of CRP.

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“…23 CRP (60 g) was incubated with 0, 0.1, 1, or 10 g phosphorylcholine (obtained from Sigma) in HEPES/Ca 2ϩ buffer for 30 minutes. Thereafter, E-LDL (500 g cholesterol) was added to each sample, and incubation continued for another 30 minutes.…”

Section: Quantitative Assessment Of Crp-binding To Ldlmentioning

confidence: 99%

Complement and Atherogenesis

Bhakdi

Torzewski

Klouche

et al. 1999

ATVB

287

110

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Abstract-Complement activation occurs in temporal correlation with the subendothelial deposition of LDL during early atherogenesis, and complement also plays a pathogenetic role in promoting lesion progression. Two lesion components have been identified that may be responsible for complement activation. First, enzymatic degradation of LDL generates a derivative that can spontaneously activate complement, and enzymatically degraded LDL (E-LDL) has been detected in the lesions. Second, C-reactive protein (CRP) colocalizes with complement C5b-9, as evidenced by immunohistological studies of early atherosclerotic lesions, so the possibility exists that this acute phase protein also fulfills a complement-activating function. Here, we report that addition of LDL and CRP to human serum did not result in significant C3 turnover. Addition of E-LDL provoked complement activation, which was markedly enhanced by CRP.Binding of CRP to E-LDL was demonstrated by sucrose flotation experiments. Binding was Ca 2ϩ -dependent and inhibitable by phosphorylcholine, and the complement-activating property of E-LDL was destroyed by treatment with phospholipase C. These results indicated that CRP binds to phosphorylcholine groups that become exposed in enzymatically degraded LDL particles. Immunohistological studies complemented these findings in showing that CRP colocalizes with E-LDL in early human atherosclerotic lesions. Thus enzymatic, nonoxidative modification of tissue-deposited LDL can be expected to confer CRP-binding capacity onto the molecule. The ensuing enhancement of complement activation may be relevant to the development and progression of the atherosclerotic lesion. Key Words: atherogenesis Ⅲ corrective protein Ⅲ complement Ⅲ LDL C omplement and C-reactive protein (CRP) are emerging as 2 components that may play important roles in atherogenesis. Early studies indicated that activated complement components 1,2 and CRP 3,4 are present in atherosclerotic lesions, and the demonstration followed that in situ C5b-9 generation occurred in temporal correlation with lipid deposition. 5 The search for a complement-activating entity led to the isolation of an LDL derivative, termed lesion complement activator (LCA), that had the capacity to activate the alternative complement pathway. 6 We are considering that the high content of free cholesterol in the LCA particles is important because unesterified cholesterol activates complement. 7 Similar lipidic moieties were isolated in other laboratories, 8,9 although their capacity to activate complement was not tested. Furthermore, fused LDL particles micromorphologically similar to LCA were visualized in extracellular location by deep freeze-etch electronmicroscopy in arteries of cholesterol-fed rabbits. 10 Collectively, these studies indicated that tissue-deposited LDL is modified extracellularly to yield lipid droplets with a high content of free cholesterol that have intrinsic complement-activating capacity.Subsequently, it was shown that LDL, but not HDL or VLDL, could be transformed...

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Rabbit and rat C-reactive proteins bind apolipoprotein B-containing lipoproteins.

Cited by 31 publications

References 21 publications

Effects of Atorvastatin on C-reactive Protein Secretions by Adipocytes in Hypercholesterolemic Rabbits

Effects of Atorvastatin on C-reactive Protein Secretions by Adipocytes in Hypercholesterolemic Rabbits

Rat C‐reactive protein activates the autologous complement system

Complement and Atherogenesis

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