Increased expression of NAMPT in PBMC from patients with acute coronary syndrome and in inflammatory M1 macrophages

Halvorsen, Bente; Espeland, Martine Z.; Andersen, Geir Øystein; Yndestad, Arne; Sagen, Ellen Lund; Rashidi, Azita; Knudsen, Eva Cecilie; Skjelland, Mona; Skagen, Karolina; Krohg‐Sørensen, Kirsten; Holm, Sverre; Ritschel, Vibeke N.; Holven, Kirsten B.; Biessen, Erik A. L.; Aukrust, Pål; Dahl, Tuva B.

doi:10.1016/j.atherosclerosis.2015.09.010

Cited by 53 publications

(29 citation statements)

References 36 publications

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“…23) In this study; we found that the levels of iNAMPT and eNAMPT secretion were significantly increased in the patients with ACS compared with the normal controls, which was consistent with the findings in patients with coronary artery disease (CAD). 24) The expression levels of NAD+, CRP and IL-6 levels in plasma of ACS patients and SIRT1 level in PBMC were higher than those in the control group, which suggesting that the up-regulation of the NAMPT/NAD+/SIRT1 signaling pathways may contribute to the inflammatory response. A study showed that NAMPT promoted the synthesis of NAD+ and activates the post transcriptional modification of SIRT on TNF molecules and promotes the expression of IL-6.…”

Section: Discussionmentioning

confidence: 85%

“…The study showed that the expression of NAMPT was up-regulated in cardiovascular disease patients; 24) however, whether it is useful or harmful is not clear. Study has shown that the down-regulation of NAMPT expression in ApoE knockout mice can promote the reverse cholesterol transport in macrophages through PPARα-LXRα-ABCA1/G1 signaling pathway and has an antiatherosclerotic effect.…”

Section: Discussionmentioning

confidence: 97%

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Nicotinamide Phosphate Transferase (NAMPT) Increases in Plasma in Patients with Acute Coronary Syndromes, and Promotes Macrophages to M2 Polarization

et al. 2018

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Atherosclerosis is an inflammatory disease; monocytes and macrophages play an important role in the progression of this disease. However, the mechanisms are not fully understood yet. Nicotinamide phosphate transferase (NAMPT) is the rate limiting enzyme in the synthesis of NAD, but extracellular NAMPT shows the characteristics of cytokines/adipokines, suggesting that it may be a link between metabolism and inflammation. In this study, we compared the expression levels of the NAMPT/NAD+/Sirt1 signaling pathway as well as NAMPT, CRP and IL-6 in the peripheral blood mononuclear cell (PBMC), and plasma in patients with acute coronary syndromes and healthy subjects, and analyzed their association with macrophage polarization. The relationship between eNAMPT and iNAMPT and the polarization of macrophages was analyzed by NAD+, NAMPT blocker, and neutralizing antibody treatment. The results showed that the expression of the NAMPT/NAD+/Sirt1 signaling pathway was up-regulated in the peripheral blood of patients with ACS. Inhibition of iNAMPT expression can reduce M1 polarization; however, there was no significant effect on eNAMPT secretion and M2 polarization. Neutralizing eNAMPT by neutralizing antibodies can reduce M2 polarization and decrease the expression levels of IL-10, IL-13, IL-4 and IL-1ra. The addition of NAD+ in the cell culture supernatant had no significant effect on the polarization of M1 but increased the M2 polarization and the expression levels of IL-10 and IL-1ra. Our findings suggested that NAMPT is involved in the pathogenesis of atherosclerosis; the increased expression of eNAMPT in ACS patients may play a protective role by the up regulation of the NAMPT/NAD+/Sirt1 signaling pathway.

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Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 97%

Nicotinamide Phosphate Transferase (NAMPT) Increases in Plasma in Patients with Acute Coronary Syndromes, and Promotes Macrophages to M2 Polarization

et al. 2018

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“…Macrophages can also exist in intermediate polarization states and switch phenotype in response to stimuli, for example the macrophage colony-stimulating factor (M-CSF) and granulocytemacrophage colony-stimulating factor (GM-CSF) polarizes monocytes to M2 and M1 macrophages, respectively [162,163]. In paper II, differentiation of primary monocytes towards macrophages was performed using M-CSF for 7 days before stimulation with either interferon (IFN)γ and LPS or interleukin (IL) 4 for M1 or M2 polarization, respectively [163,164].…”

Section: Differentiation Of Macrophagesmentioning

confidence: 99%

“…Verification of macrophage polarization by this protocol has been done previously using mRNA expression of markers like tumor necrosis factor (TNF) and IL-6 for M1 and CD163 and peroxisome proliferator-activated receptor γ for M2 [164]. Primary monocytes have previously been shown not to secrete legumain, whereas M-CSF-differentiation of macrophages resulted in substantial secretion of prolegumain to the conditioned media [36].…”

Section: Differentiation Of Macrophagesmentioning

confidence: 99%

Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions

et al. 2017

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“…Nicotinamide phosphoribosyltransferase (NAMPT) is a crucial enzyme in the cyclic biosynthetic pathway of nicotinamide adenine dinucleotide (NAD), serving as the catalyzer of the generation from nicotinamide (NM) to nicotinamide mononucleotide (NMN) 5 . Indeed, it has been postulated that NAMPT may participate in the regulation of inflammation and is responsible for many inflammatory diseases 6,7 . NAMPT was also involved in the regulation of apoptosis 8‐10 .…”

Section: Introductionmentioning

confidence: 99%

Neuroprotective effects of FK866 against traumatic brain injury: Involvement of p38/ERK pathway

Tan

Chen

Ren

et al. 2020

Ann Clin Transl Neurol

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Objective: FK866 is an inhibitor of nicotinamide phosphoribosyltransferase (NAMPT), which exhibits neuroprotective effects in ischemic brain injury. However, in traumatic brain injury (TBI), the role and mechanism of FK866 remain unclear. The present research was aimed to investigate whether FK866 could attenuate TBI and clarified the underlying mechanisms. Methods: A controlled cortical impact model was established, and FK866 at a dose of 5 mg/kg was administered intraperitoneally at 1 h and 6 h, then twice per day post-TBI until sacrifice. Brain water content, Evans blue dye extravasation, modified neurological severity scores (mNSS), Morris water maze test, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining, and western blot were performed. Results: The results demonstrated that FK866 significantly mitigated the brain edema, blood-brain barrier (BBB) disruption, and ameliorated the neurological function post-TBI. Moreover, FK866 decreased the number of Iba-1-positive cells, GFAP-positive astrocytes, and AQP4-positive cells. FK866 reduced the protein levels of proinflammatory cytokines and inhibited NF-jB from translocation to the nucleus. FK866 upregulated the expression of Bcl-2, diminished the expression of Bax and caspase 3, and the number of apoptotic cells. Moreover, p38 MAPK and ERK activation were significantly inhibited by FK866. Interpretation: FK866 attenuated TBI-induced neuroinflammation and apoptosis, at least in part, through p38/ERK MAPKs signaling pathway. 742

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Increased expression of NAMPT in PBMC from patients with acute coronary syndrome and in inflammatory M1 macrophages

Abstract: Based on our in vivo and in vitro findings we suggest that NAMPT could contribute to systemic and plaque inflammation in atherosclerotic disorders at least partly through effect on macrophages.

Cited by 53 publications

References 36 publications

Nicotinamide Phosphate Transferase (NAMPT) Increases in Plasma in Patients with Acute Coronary Syndromes, and Promotes Macrophages to M2 Polarization

Nicotinamide Phosphate Transferase (NAMPT) Increases in Plasma in Patients with Acute Coronary Syndromes, and Promotes Macrophages to M2 Polarization

Glycosylation is important for legumain localization and processing to active forms but not for cystatin E/M inhibitory functions

Neuroprotective effects of FK866 against traumatic brain injury: Involvement of p38/ERK pathway

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