title: Exaggerated inflammation and monocytosis associate with diastolic dysfunction in heart failure with preserved ejection fraction: evidence of M2 macrophage activation in disease pathogenesis.
abstract: BACKGROUND
  Heart failure with preserved ejection fraction (HFPEF) is a major health problem associated with myocardial leukocyte infiltration, inflammation, and fibrosis. Monocyte and macrophage subsets play a role in HFPEF but have not been studied. We analyzed peripheral blood monocyte phenotype and plasma markers of monocyte activation in patients with HFPEF, asymptomatic LV diastolic dysfunction (aLVDD), and asymptomatic hypertension (aHTN).
  
  
  RESULTS
  Peripheral blood was collected from 23 aHTN, 30 aLVDD, and 30 HFPEF patients. Peripheral cytokines of classic/pro-inflammatory (tumor necrosis factor alpha, interleukin (IL) 12, IL-6, monocyte chemoattractant protein 1, C-X-C motif chemokine 10) and alternative/anti-inflammatory monocytes (chemokine-C-C motif ligand (CCL) 17, CCL-18, soluble CD163) were increased in aLVDD and HFPEF. Peripheral blood mononuclear cells and monocytes were purified and surface-stained for CD14, CD16, CD163, and CD206. Peripheral monocyte percentage was increased in aLVDD and HFPEF and correlated with echocardiographic LVDD indices. Classic/pro-inflammatory monocyte numbers were increased in aLVDD and HFPEF, and alternative/anti-inflammatory monocyte numbers were increased in HFPEF. CD163 M2-macrophage receptor was reduced in HFPEF. Culture of healthy donor monocytes (n = 3) with HFPEF patient-derived sera (n = 6) promoted M2 macrophage features as evidenced by altered morphology and genes (CD206, IL-10).
  
  
  CONCLUSIONS
  Increased peripheral inflammation, monocytosis, and monocyte differentiation to anti-inflammatory/profibrotic M2 macrophages likely associate with HFPEF and its precedent asymptomatic LVDD phase.
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Nadezhda
authors.initials: N
authors.lastname: Glezeva
authors.affiliation: Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors.forename: Victor
authors.initials: V
authors.lastname: Voon
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland.
authors.forename: Chris
authors.initials: C
authors.lastname: Watson
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors.forename: Stephen
authors.initials: S
authors.lastname: Horgan
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland; Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors.forename: Kenneth
authors.initials: K
authors.lastname: McDonald
authors.affiliation: Heart Failure Unit, St Vincent's University Hospital Healthcare Group, Elm Park, Dublin, Ireland.
authors.forename: Mark
authors.initials: M
authors.lastname: Ledwidge
authors.affiliation: Conway Institute of Biomolecular and Biomedical Research, School of Medicine and Medical Science, University College Dublin, Dublin, Ireland. Electronic address: john.baugh@ucd.ie.
authors.forename: John
authors.initials: J
authors.lastname: Baugh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D054144:Heart Failure, Diastolic / Q000097:blood* / Q000175:diagnosis*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis; D018836:Inflammation Mediators / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008262:Macrophage Activation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D013318:Stroke Volume / Q000502:physiology*
chemical_list: D018836:Inflammation Mediators
keywords: Monocytes; heart failure with preserved ejection fraction; hypertension; inflammation