title: Circulating CD14+ and CD14highCD16- classical monocytes are reduced in patients with signs of plaque neovascularization in the carotid artery.
abstract: Monocytes are known to play a key role in the initiation and progression of atherosclerosis and contribute to plaque destabilization through the generation of signals that promote inflammation and neoangiogenesis. In humans, studies investigating the features of circulating monocytes in advanced atherosclerotic lesions are lacking.
  
  
  
  Patients (mean age 69 years, 56% males) with intermediate asymptomatic carotid stenosis (40-70% in diameter) were evaluated for maximal stenosis in common carotid artery, carotid bulb and internal carotid artery, overall disease burden as estimated with total plaque area (TPA), greyscale and neovascularization in 244 advanced carotid plaques. Absolute counts of circulating CD14+ monocytes, of classical (CD14highCD16-), intermediate (CD14highCD16+) and non-classical (CD14lowCD16+) monocytes and HLA-DR+ median fluorescence intensity for each subset were evaluated with flow cytometry.
  
  
  
  No correlation was found between monocytes and overall atherosclerotic burden, nor with high sensitivity C-reactive protein (hsCRP) or interleukin-6 (IL-6). In contrast, plaque signs of neovascularization were associated with significantly lower counts of circulating CD14+ monocytes (297 versus 350 cells/mm3, p = 0.039) and of classical monocytes (255 versus 310 cells/mm3, p = 0.029).
  
  
  
  Neovascularized atherosclerotic lesions selectively associate with lower blood levels of CD14+ and CD14highCD16- monocytes independently of systemic inflammatory activity, as indicated by normal hsCRP levels. Whether the reduction of circulating CD14+ and CD14highCD16- monocytes is due to a potential redistribution of these cell types into active lesions remains to be explored.
authors.affiliation: Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy; De Gasperis Cardio Center, Niguarda Ca' Granda Hospital, Milan, Italy. Electronic address: ammirati.enrico@hsr.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Ammirati
authors.affiliation: Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy. Electronic address: moroni@studenti.unisr.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Moroni
authors.affiliation: Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Magnoni
authors.affiliation: FRACTAL - Flow cytometry Resource Advanced Cytometry Technical Applications Laboratory, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Di Terlizzi
authors.affiliation: FRACTAL - Flow cytometry Resource Advanced Cytometry Technical Applications Laboratory, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Villa
authors.affiliation: Nestlé Institute of Health Sciences, Biobanking & Flow Cytometry Core EPFL, Innovation Park Bâtiment H, Lausanne, Switzerland.
authors.forename: Federico
authors.initials: F
authors.lastname: Sizzano
authors.affiliation: Nestlé Institute of Health Sciences, Biobanking & Flow Cytometry Core EPFL, Innovation Park Bâtiment H, Lausanne, Switzerland.
authors.forename: Alessio
authors.initials: A
authors.lastname: Palini
authors.affiliation: Center SISA for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Garlaschelli
authors.affiliation: Hematology and Blood Transfusion Service, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Tripiciano
authors.affiliation: Department of Rheumatology, Istituto Ortopedico Gaetano Pini, Milan, Italy.
authors.forename: Isabella
authors.initials: I
authors.lastname: Scotti
authors.affiliation: IRCCS - Multimedica Hospital, Sesto San Giovanni, Italy; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy.
authors.forename: Alberico Luigi
authors.initials: AL
authors.lastname: Catapano
authors.affiliation: Unit of Internal Medicine & Clinical Immunology, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
authors.forename: Angelo A
authors.initials: AA
authors.lastname: Manfredi
authors.affiliation: Center SISA for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
authors.forename: Giuseppe Danilo
authors.initials: GD
authors.lastname: Norata
authors.affiliation: Cardiothoracic Department, San Raffaele Scientific Institute and Vita-Salute University, Milan, Italy.
authors.forename: Paolo G
authors.initials: PG
authors.lastname: Camici
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D002339:Carotid Arteries / Q000000981:diagnostic imaging / Q000473:pathology*; D016893:Carotid Stenosis / Q000097:blood* / Q000000981:diagnostic imaging / Q000473:pathology; D003287:Contrast Media / Q000008:administration & dosage; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood; D015850:Interleukin-6 / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D009389:Neovascularization, Pathologic; D010743:Phospholipids / Q000008:administration & dosage; D058226:Plaque, Atherosclerotic; D017452:Receptors, IgG / Q000097:blood*; D012720:Severity of Illness Index; D013459:Sulfur Hexafluoride / Q000008:administration & dosage; D018616:Ultrasonography, Doppler, Duplex
chemical_list: D015415:Biomarkers; D003287:Contrast Media; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D010743:Phospholipids; D017452:Receptors, IgG; C420843:contrast agent BR1; D002097:C-Reactive Protein; D013459:Sulfur Hexafluoride
keywords: Carotid atherosclerosis; Classical monocytes; Contrast enhanced ultrasound; Monocytes subsets; Plaque neovascularization