title: Increased haematopoietic activity in patients with atherosclerosis.
abstract: Experimental work posits that acute ischaemic events trigger haematopoietic activity, driving monocytosis, and atherogenesis. Considering the chronic low-grade inflammatory state in atherosclerosis, we hypothesized that haematopoietic hyperactivity is a persistent feature in cardiovascular disease (CVD). Therefore, we aimed to assess the activity of haematopoietic organs and haematopoietic stem and progenitor cells (HSPCs) in humans.
  
  
  
  First, we performed 18F-fluorodeoxyglucose positron emission tomographic (18F-FDG PET) imaging in 26 patients with stable atherosclerotic CVD (ischaemic event >12 months ago), and 25 matched controls. In splenic tissue, 18F-FDG uptake was 2.68 ± 0.65 in CVD patients vs. 1.75 ± 0.54 in controls (1.6-fold higher; P< 0.001), and in bone marrow 3.20 ± 0.76 vs. 2.72 ± 0.46 (1.2-fold higher; P = 0.003), closely related to LDL cholesterol levels (LDLc, r = 0.72). Subsequently, we determined progenitor potential of HSPCs harvested from 18 patients with known atherosclerotic CVD and 30 matched controls; both groups were selected from a cohort of cancer patients undergoing autologous stem cell transplantation. In CVD patients, the normalized progenitor potential, expressed as the number of colony-forming units-granulocyte/monocyte (CFU-GM) colonies/CD34+ cell, was 1.6-fold higher compared with matched controls (P < 0.001). Finally, we assessed the effects of native and oxidized lipoproteins on HSPCs harvested from healthy donors in vitro. Haematopoietic stem and progenitor cells displayed a 1.5-fold increased CFU-GM capacity in co-culture with oxidized LDL in vitro (P = 0.002), which was inhibited by blocking oxidized phospholipids via E06 (P = 0.001).
  
  
  
  Collectively, these findings strengthen the case for a chronically affected haematopoietic system, potentially driving the low-grade inflammatory state in patients with atherosclerosis.
authors.affiliation: Department of Vascular Medicine, AMC, Room F4-146, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Fleur M
authors.initials: FM
authors.lastname: van der Valk
authors.affiliation: Department of Hematopoiesis, Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carlijn
authors.initials: C
authors.lastname: Kuijk
authors.affiliation: Department of Vascular Medicine, AMC, Room F4-146, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Simone L
authors.initials: SL
authors.lastname: Verweij
authors.affiliation: Department of Vascular Medicine, AMC, Room F4-146, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Lotte C A
authors.initials: LCA
authors.lastname: Stiekema
authors.affiliation: Department of Vascular Medicine, AMC, Room F4-146, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Y
authors.initials: Y
authors.lastname: Kaiser
authors.affiliation: Department of Hematology, AMC, Amsterdam, The Netherlands.|Department of Immunopathology, Sanquin Research, Amsterdam, The Netherlands.
authors.forename: Sacha
authors.initials: S
authors.lastname: Zeerleder
authors.affiliation: Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Nahrendorf
authors.affiliation: Department of Hematopoiesis, Sanquin Research, and Landsteiner Laboratory, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Carlijn
authors.initials: C
authors.lastname: Voermans
authors.affiliation: Department of Vascular Medicine, AMC, Room F4-146, PO Box 22660, 1100 DD, Amsterdam, The Netherlands.
authors.forename: Erik S G
authors.initials: ESG
authors.lastname: Stroes
mesh_terms: D001853:Bone Marrow / Q000502:physiology; D016022:Case-Control Studies; D002478:Cells, Cultured; D008078:Cholesterol, LDL / Q000502:physiology; D003324:Coronary Artery Disease / Q000473:pathology*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006410:Hematopoiesis / Q000502:physiology*; D006411:Hematopoiesis, Extramedullary / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D000072078:Positron Emission Tomography Computed Tomography; D019275:Radiopharmaceuticals; D012307:Risk Factors; D061205:Vascular Calcification / Q000473:pathology*
chemical_list: D008078:Cholesterol, LDL; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: Atherosclerosis; Haematopoietic stem and progenitor cells; Imaging; Inflammation; Oxidized lipoproteins