C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation

Cirillo, Plinio; Golino, Paolo; Calabrò, Paolo; Calı̀, Gaetano; Ragni, Maurizio; Rosa, Salvatore De; Cimmino, Giovanni; Pacileo, Mario; Palma, Raffaele De; Forte, L. A.; Gargiulo, Annarita; Corigliano, Fabio Granato; Angri, Valeria; Spagnuolo, Raffaele; Nitsch, Lucio; Chiariello, Massimo

doi:10.1016/j.cardiores.2005.05.010

Cited by 142 publications

(116 citation statements)

References 45 publications

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“…Furthermore, we have previously shown in vivo that CRP augments NFκb activity in rat pouch macrophages. In this paper, in support of the work of Cirillo et al [36], we show that inhibition of NFκb activity with CAPE, resulted in significant inhibition of CRP-induced TF activity in vivo. Furthermore, using three scavengers of ROS, we demonstrate a link between CRPinduced superoxide release and TF activity, since all three inhibitors significantly abrogate CRP-induced TF activity.…”

Section: Discussionsupporting

confidence: 89%

“…In addition, CRP also induced TF expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time PCR. Activation of the transcription factor, NFκb, by CRP was demonstrated by EMSA and they also demonstrated suppression of TF expression by the NFκb inhibitor, pyrrolidine-dithiocarbamate ammonium [12,36]. In rat pouch macrophages, in vivo, we show for the first time that CRP-induced TF is inhibited by inhibitors to p38MAPK and JNK, but not ERK inhibitor.…”

Section: Discussionmentioning

confidence: 58%

“…Previously, CRP has been shown to induce procoagulant activity as observed by increased endothelial PAI-1 and decreased tPA [3]. Cirillo et al [36] demonstrated that incubation of endothelial cells and smooth muscle cells with CRP resulted in a dose-dependent activation of cell proliferation, which was mediated by activation of the ERK 1/2 pathway. In addition, CRP also induced TF expression in both cell types in a dose-dependent fashion, exerting its effect at the transcriptional level, as demonstrated by semiquantitative and by real-time PCR.…”

Section: Discussionmentioning

confidence: 99%

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C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

et al. 2009

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C-reactive protein (CRP), the prototypic marker of inflammation, is a cardiovascular risk marker and recent in vitro studies suggest that it may promote atherogenesis. CRP promotes oxidative stress in vitro and induces tissue factor (TF) release. However, there is a paucity of data examining the effects of CRP on oxidative stress and tissue factor procoagulant activity (PCA) in vivo. Thus, we tested the effects of CRP administration on superoxide anion release and tissue factor activity and examined mechanistic pathways using a rat sterile air pouch model. Intraperitoneal administration of CRP (20 mg/kg body weight) compared to human serum albumin (HuSA) increased superoxide anion release and tissue factor activity from peritoneal macrophages in vivo (p < 0.01). This was confirmed using intrapouch administration of CRP (25 μg/mL) compared to HuSA. Pretreatment with reactive oxygen species (ROS) scavengers or protein kinase C (PKC) inhibitor significantly abrogated CRP-induced superoxide anion release and tissue factor activity. Pretreatment with extracellular signal-regulated kinase (ERK) and Jun N-terminal kinase (JNK) inhibitors, but not p38 mitogen-activated protein kinase (p38MAPK) significantly decreased CRP-induced superoxide anion release from macrophages in vivo. CRP-induced tissue factor activity in vivo was abrogated by pretreatment with inhibitors to p38MAPK, JNK and NFκb (nuclear factor-κb), but not ERK. Antibodies to Fc gamma receptors, CD32 and CD64 resulted in significant reduction in CRP-induced superoxide and tissue factor activity in vivo. Thus, CRP appears to induce oxidative stress in vivo by stimulating NADPH oxidase via PKC, ERK and JNK phosphorylation, and induces tissue factor PCA in vivo via upregulation of PKC, p38MAPK, JNK, ROS and NFκb. CRP-induced ROS appears to precede tissue factor release. These effects are abrogated by blocking Fc gamma receptors, CD32 and CD64. This in vivo demonstration provides further evidence for a role for CRP in atherothrombosis.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 99%

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C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

et al. 2009

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“…15 Therefore CRP might play a role not only in inflammation but also in atherothrombosis. 16,17 In this investigation we looked at the two phenomena from the same angle and wanted to rest our hypothesis in that direction. We had hypothesized that if CRP plays an important role in thrombus development we should be detecting high levels of hs-CRP on admission day in patients with left ventricular thrombus (LVA).…”

Section: Discussionmentioning

confidence: 99%

C-Reactive Protein is not an Independent Risk Factor for Ventricular Thrombus

Demïrtürk¹,

Gülcan²,

Çoşkun³

et al. 2012

JIUMF

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C-reactive protein (CRP) is a standard and widely used acute phase reactant. It is a prototypic marker of inflammation and an adverse event indicator. Elevated CRP levels have been found to be correlated with higher risk for potential adverse cardiac events in patients with acute myocardial infarction, stable and unstable coronary artery disease. However the relationship between presence of left ventricular thrombus (LVT) and levels of CRP have not been investigated in the patients undergoing left ventricular restorative operations. In order to investigate the correlation and seek out the ability of the predictive value of CRP levels in patients with left ventricular aneurysm (LVA), we studied operational and biochemical findings of our patients with LVA, who underwent coronary revascularization operations. We found that CRP levels do not predict presence of LVT.

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“…Both the p50 and p60 subunits of NFkB play a role in the transcription of CRP, 29 which appeared to have proatherogenic properties through upregulation of expression of AT 1 receptor 30 and activation of vascular smooth muscle cells in some studies. 31,32 Over 30 studies have reported that higher plasma levels of CRP are associated with higher risks of CHD, 33 but other studies have not been to able to confirm these associations, 34,35 and there is uncertainty as to whether these associations are causal. Fibrinogen has been observed to regulate to NFkB activation and the expression of chemokines in vascular endothelial cells, 36 but for it too there is uncertainty about the nature of the relationship with vascular disease.…”

Section: Marker and Genotypementioning

confidence: 99%

The exon 1–8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6946 cases and 2720 controls from a United Kingdom population

Bennett

Clarke

et al. 2008

Eur J Hum Genet

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The proteasome system is a proteolytic pathway that regulates the expression of genes involved in inflammation. Polymorphisms in the gene encoding subunit a type 6 (PSMA6) -in particular the rs1048990 exon 1-8C/G SNP -have been implicated with susceptibility to myocardial infarction (MI) in a Japanese study. We examined whether several polymorphisms in the PSMA6 gene were related to MI risk in 6946 nonfatal MI cases and 2720 unrelated controls in a UK population. The homozygous GG genotype for rs1048990 was much less frequent in this UK population than in the Japanese population (2.1 vs 8.9%), and was associated with an odds ratio (OR) for MI of 1.09 (95% confidence interval (CI): 0.98 -1.21) per G allele in a co-dominant genetic model and 1.32 (95% CI: 0.90-1.93) in a recessive genetic model. Although not statistically significant, these results for this variant are still consistent with the Japanese hypothesisgenerating study. Our findings, when taken together with four other studies (including the hypothesisgenerating one), yielded a combined OR for MI of 1.15 (95% CI: 1.08 -1.21) per G allele in a co-dominant model and 1.38 (95% CI: 1.22 -1.57) for the GG genotype in a recessive model. Larger studies involving more than 10 000 disease cases would be required to further elucidate the role of this variant for susceptibility to MI. However, given the rarity of this variant in Caucasians, the attributable risk of rs1048990 for MI is unlikely to be great in western populations.

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C-reactive protein induces tissue factor expression and promotes smooth muscle and endothelial cell proliferation

Cited by 142 publications

References 45 publications

C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

C-reactive protein stimulates superoxide anion release and tissue factor activity in vivo

C-Reactive Protein is not an Independent Risk Factor for Ventricular Thrombus

The exon 1–8C/G SNP in the PSMA6 gene contributes only a small amount to the burden of myocardial infarction in 6946 cases and 2720 controls from a United Kingdom population

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