CRP promotes monocyte-endothelial cell adhesion via Fcγ receptors in human aortic endothelial cells under static and shear flow conditions

Devaraj, Sridevi; Davis, Benjamin; Simon, Scott I.; Jialal, Ishwarlal

doi:10.1152/ajpheart.00150.2006

Cited by 90 publications

(78 citation statements)

References 33 publications

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“…OxLDL and CRP stimulate activated macrophages to release TNF-α, IL-6 and other cytokines that induce vascular and macrophage activation, thus leading to inflammation (26,27). According to the present study, the triple combination reduces the release of these cytokines, which may retard the inflammatory process associated with atherosclerosis.…”

Section: Discussionmentioning

confidence: 53%

The combination of CRP isoforms with oxLDL decreases TNF-α and IL-6 release by U937-derived macrophages

2017

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Abstract. C-reactive protein (CRP) and oxidized low density lipoprotein (oxLDL) serve major roles at both early and advanced stages of atherosclerosis. CRP exists in two isoforms, monomeric (m) and pentameric (p), that bring about pro-or anti-inflammatory effects in macrophages. In addition, CRP may form a complex with oxidized low-density lipoprotein (oxLDL) via phosphatidylcholine, thus decreasing its pro-inflammatory effects within macrophages. The aim of the present study was to investigate the single and the combined effects of mCRP, pCRP and oxLDL on U937-derived macrophages. In the current study, U937-derived macrophages were treated in vitro with different combinations of CRP isoforms with or without oxLDL. The levels of major inflammatory cytokines [interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF)-α] along with the production of reactive oxygen species (ROS) were determined. TNF-α and IL-6 levels were significantly decreased (P<0.05) by the effect of mCRP and pCRP combined with oxLDL. No significant changes were observed in IL-1β, IL-8 or ROS levels.

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Section: Discussionmentioning

confidence: 53%

The combination of CRP isoforms with oxLDL decreases TNF-α and IL-6 release by U937-derived macrophages

2017

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“…We have previously shown that blocking of CD32/CD64 in endothelial cells abrogate effects of CRP [5,10,11,24,28]. Also, recently we showed that CRP induces superoxide anion release in endothelial cells and promotes eNOS uncoupling, this is reversed by inhibition of CD32 and CD64 [5].…”

Section: Discussionmentioning

confidence: 91%

“…Previously, CRP has been shown to mediate its biological effects in endothelial cells and monocyte-macrophages via CD32 and CD64 [3][4][5][10][11][12][24][25][26][27][28]. Thus, we examined the effects of antibodies to CD16, CD32 and CD64 on CRP-induced superoxide anion release and tissue factor activity.…”

Section: Mechanistic Insights For Crp-mediated Superoxide Release Andmentioning

confidence: 99%

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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“…There is emerging evidence of CRP as a direct and causative factor contributing to development of atherosclerosis (46,47). CRP increases monocyte adhesion to human endothelial cells under flow conditions (48) and is released from vulnerable plaques, where it co-localises with macrophages, oxLDL, and complement factors (49)(50)(51). In human plasma, CRP exists as a cyclic, disc-shaped pentamer of 115 kDa (pentameric pCRP) (40) or as a monomeric or modified mCRP (52,53).…”

Section: C-reactive Protein (Crp)mentioning

confidence: 99%

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

Müller¹,

Chatterjee²,

Rath³

et al. 2015

Thromb Haemost

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SummaryPlatelets play a pivotal role in chronic inflammation leading to progression of atherosclerosis and acute coronary events. Recent discoveries on novel mechanisms and platelet-dependent inflammatory targets underpin the role of platelets to maintain a chronic inflammatory condition in cardiovascular disease. There is strong and clinically relevant crosslink between chronic inflammation and platelet activation. Antiplatelet therapy is a cornerstone in the prevention and treatment of acute cardiovascular events. The benefit of antiplatelet agents has mainly been attributed to their direct anti-aggregatory impact. Some anti-inflammatory off-target effects have also been described. However, it is unclear whether these effects are secondary due to inhibition of platelet activation or are caused by direct distinct mechanisms interfering with inflammatory pathways. This article will highlight novel platelet associated targets that contribute to inflammation in cardiovascular disease and elucidate mechanisms by which currently available antiplatelet agents evolve anti-inflammatory capacities, in particular by carving out the differential mechanisms directly or indirectly affecting platelet mediated inflammation. It will further illustrate the prognostic impact of antiplatelet therapies by reducing inflammatory marker release in recent cardiovascular trials.

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CRP promotes monocyte-endothelial cell adhesion via Fcγ receptors in human aortic endothelial cells under static and shear flow conditions

Cited by 90 publications

References 33 publications

The combination of CRP isoforms with oxLDL decreases TNF-α and IL-6 release by U937-derived macrophages

The combination of CRP isoforms with oxLDL decreases TNF-α and IL-6 release by U937-derived macrophages

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

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

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