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

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

doi:10.1016/j.atherosclerosis.2015.09.010

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

Atherosclerosis. 2015 Nov;243(1):204-10. doi: 10.1016/j.atherosclerosis.2015.09.010. Epub 2015 Sep 8.

Authors

Bente Halvorsen¹, Martine Z Espeland², Geir Øystein Andersen³, Arne Yndestad⁴, Ellen Lund Sagen², Azita Rashidi⁵, Eva C Knudsen⁶, Mona Skjelland⁷, Karolina R Skagen⁷, Kirsten Krohg-Sørensen⁸, Sverre Holm⁵, Vibeke Ritschel⁶, Kirsten B Holven⁹, Erik A L Biessen¹⁰, Pål Aukrust¹¹, Tuva B Dahl¹²

Affiliations

¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway.
² Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
³ Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Heart Failure, University of Oslo, Oslo, Norway.
⁴ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Center for Heart Failure, University of Oslo, Oslo, Norway.
⁵ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁶ Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway; Center for Clinical Heart Research, Oslo University Hospital Ullevål, Oslo, Norway.
⁷ Department of Neurology, Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁸ Department of Thoracic and Cardiovascular Surgery Oslo University Hospital Rikshospitalet, Oslo, Norway.
⁹ Department of Nutrition, Institute for Basic Medical Sciences, University of Oslo, Norway.
¹⁰ Experimental Vascular Pathology Group, Department of Pathology, CARIM, Maastricht University Medical Center, Maastricht, The Netherlands.
¹¹ Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Disease, Oslo University Hospital Rikshospitalet, Oslo, Norway.
¹² Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; K.G. Jebsen Inflammation Research Center, University of Oslo, Oslo, Norway. Electronic address: tuvad@rr-research.no.

PMID: 26402139
DOI: 10.1016/j.atherosclerosis.2015.09.010

Abstract

Aim: The aim of the present study were to elucidate the role of NAMPT in atherosclerosis, by examine NAMPT expression in peripheral blood mononuclear cells (PBMC) in patients with coronary artery disease (CAD) and healthy controls and by examining the regulation and effect of NAMPT on macrophage polarization, hypothesizing that it could influence the polarization to inflammatory and resolving macrophages.

Method and results: We analyzed RNA levels of NAMPT in PBMC from CAD and healthy controls and found NAMPT to be increased in PBMC from patients with acute coronary syndrome (n = 39) compared to healthy controls (n = 20) and patients with stable CAD (n = 22). Within the PBMC NAMPT was correlated to several inflammatory cytokines and the antioxidant enzyme superoxide dismutase 2. In vitro cell experiments revealed that NAMPT is increased both intracellular and extracellular in inflammatory M1 macrophages compared to in anti-inflammatory M2 macrophages. In addition, inhibiting NAMPT enzymatic activity inhibited M1 polarization in macrophages.

Conclusion: 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.

Keywords: Acute coronary syndrome; Atherosclerosis; Inflammation; Macrophage polarization; NAMPT.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Coronary Syndrome / blood*
Aged
Animals
Biomarkers / metabolism
Bone Marrow Cells / cytology
Cell Line
Coronary Artery Disease / blood*
Cytokines / metabolism*
Female
Gene Expression Regulation
Humans
Inflammation
Leukocytes, Mononuclear / cytology*
Leukocytes, Mononuclear / metabolism
Macrophages / cytology*
Male
Mice
Mice, Inbred C57BL
Middle Aged
Monocytes / cytology
Nicotinamide Phosphoribosyltransferase / metabolism*
Oxidation-Reduction
Phenotype
Plaque, Atherosclerotic / metabolism
RNA / metabolism

Substances

Biomarkers
Cytokines
RNA
Nicotinamide Phosphoribosyltransferase
nicotinamide phosphoribosyltransferase, human