title: Abnormal plasma levels of different angiogenic molecules are associated with different clinical manifestations in patients with systemic sclerosis.
abstract: OBJECTIVE
  Systemic Sclerosis (SSc) is characterized by a microvascular damage due to an impairment of different angiogenic and angiostatic factors. Aim of this study was to measure plasma levels of nine molecules involved in these vascular processes in a group of SSc patients, respect to healthy controls (NC).
  
  
  METHODS
  Sixty-five patients (M/F = 2/63; mean age = 57.29 yrs; mean disease duration = 9,63 yrs) with established SSc according to ARA criteria, and sixteen age- and sex-matched NC were enrolled. Plasma levels of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2), platelet derived growth factor- bb (PDGF-BB), platelet endothelial cellular adhesion molecule-1 (PECAM-1), leptin, hepathocyte growth factor (HGF), follistatin, granulocyte-colony stimulating factor (G-CSF) and interleukin 8 (IL-8) were measured using commercially available immunoassay kits (Human Angiogenesis 9-Plex Panel, Bio-Rad Laboratories).
  
  
  RESULTS
  We detected a significant increase of Ang-2 (median value 1315.4 pg/ml vs 538.73 pg/ml; p=0.0292), HGF (median value 2886.16 pg/ml vs 1296.16 pg/ml; p=0.0001), IL-8 (median value 32.22 pg/ml vs 16.86 pg/ml; p=0.02), leptin (median value 32589,1 pg/mg vs 10679.61 pg/ml; p=0.0065), PDGF-BB (median value 7258.6 pg/ml vs 2913.44 pg/ml; p=0.0005), PECAM-1(median value 21681.81 pg/ml vs 10354.53 pg/ml; p=0.0003) and VEGF (median value 236.72 pg/ml vs 122.905 pg/ml; p=0.0073) in patients with SSc respect to NC. Higher levels of PDGF-BB (p=0.03) and PECAM-1 (p=0.05) were found in patients with digital ulcers while lower levels of PECAM-1 were found in patients with pulmonary hypertension (PH). Besides levels of IL-8 were higher in patients with PH (p=0.04) and lower in those with pulmonary fibrosis (p=0.5), while levels of Ang-2 were higher in those with a 'late' nailfold video-capillaroscopy (NVC) pattern respect to those with an 'early/active' one (p=0.05). Moreover, plasma levels of VEGF (p=0.02) and PDGF-BB (p= 0.04) were significantly higher in those patients positive for anti-topoisomerase 1 antibodies.
  
  
  CONCLUSIONS
  Our findings show significantly higher circulating levels of seven angiogenic parameters in SSc patients, thus reflecting the disregulation of endothelium in this disease. Abnormal levels of these molecules may be considered an attempt for compensatory although ineffective mechanisms of vascular function, leading to the development of the main clinical manifestations of SSc.
authors.affiliation: Rheumatological Unit, Department of Internal Medicine and Clinical Specialities, University of Rome 'Sapienza', Rome, Italy. valeria.riccieri@uniroma1.it
authors.forename: Valeria
authors.initials: V
authors.lastname: Riccieri
authors.forename: Katia
authors.initials: K
authors.lastname: Stefanantoni
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Vasile
authors.forename: Valeria
authors.initials: V
authors.lastname: Macrì
authors.forename: Iliana
authors.initials: I
authors.lastname: Sciarra
authors.forename: N
authors.initials: N
authors.lastname: Iannace
authors.forename: Cristiano
authors.initials: C
authors.lastname: Alessandri
authors.forename: Guido
authors.initials: G
authors.lastname: Valesini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D043925:Angiogenesis Inducing Agents / Q000097:blood*; D020533:Angiogenesis Inhibitors / Q000097:blood*; D000077214:Becaplermin; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000097:blood; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D020678:Microscopic Angioscopy; D055806:Microvessels / Q000473:pathology / Q000503:physiopathology; D008875:Middle Aged; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000097:blood; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D011928:Raynaud Disease / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology*; D012595:Scleroderma, Systemic / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D043925:Angiogenesis Inducing Agents; D020533:Angiogenesis Inhibitors; D016209:Interleukin-8; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D042461:Vascular Endothelial Growth Factor A; D016179:Granulocyte Colony-Stimulating Factor; D000077214:Becaplermin; D017228:Hepatocyte Growth Factor