title: Histological and transcriptional study of angiogenesis and lymphangiogenesis in uninvolved skin, acute pinpoint lesions and established psoriasis plaques: an approach of vascular development chronology in psoriasis.
abstract: BACKGROUND
  Dysregulation of angiogenesis and lymphangiogenesis could participate in psoriasis pathogenesis. Analysis of nascent psoriasis lesions should help at identifying early vascular anomalies.
  
  
  OBJECTIVE
  To analyse vascular development, angiogenesis and lymphangiogenesis markers expression in uninvolved skin in psoriatic patients (N), early psoriasis lesions or pinpoints (PP) and psoriasis plaques (PSO).
  
  
  METHODS
  Skin biopsies were taken in 17 patients in N and in PSO and/or PP. The mRNA steady-state level of angiogenesis and lymphangiogenesis markers was measured by RT-PCR. Immunohistochemistry was performed for von Willebrand factor, podoplanin, Ki-67 and VEGFR3. Blood (BV) and lymphatic (LV) vessels expansion was measured by computer-assisted morphometry.
  
  
  RESULTS
  Clinical and epidermal aspects indicated that PP are intermediate between N and PSO. While total BV area was already increased in PP similarly to PSO as compared to N, LV area in PP was intermediate between N and PSO. Mean LV size was identical in N and PP and increased in PSO, mean BV size in PP being intermediate between N and PSO. VEGF-A 189 variant was increased in PP as compared to N and PSO. As compared to N, angiogenesis markers (VEGF-A isoforms, PlGF, VEGFR2, NRP-1), VEGF-C and NRP-2 were similarly increased in PP and PSO. Keratin 16 and the lymphangiogenesis markers (VEGFR3, prox-1) were intermediate in PP.
  
  
  CONCLUSIONS
  These data suggest that the expansion of lymphatic vessels occurs after blood vascular development in psoriasis. Expansion of BV in PP could be followed by vessel enlargement during progression to PSO, in parallel with a decreased VEGF-A 189/VEGF-A 121 balance in plaques.
authors.affiliation: Department of Dermatology, University Hospital of Liège, Belgium. audrey.henno@gmail.com
authors.forename: Audrey
authors.initials: A
authors.lastname: Henno
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Charles A
authors.initials: CA
authors.lastname: Lambert
authors.forename: Christophe
authors.initials: C
authors.lastname: Deroanne
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Charles
authors.initials: C
authors.lastname: Lapière
authors.forename: Michel
authors.initials: M
authors.lastname: de la Brassinne
authors.forename: Betty V
authors.initials: BV
authors.lastname: Nusgens
authors.forename: Alain
authors.initials: A
authors.lastname: Colige
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D053536:Keratin-16 / Q000378:metabolism; D042583:Lymphangiogenesis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D018919:Neovascularization, Physiologic; D039942:Neuropilin-1 / Q000378:metabolism; D011565:Psoriasis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012339:RNA, Ribosomal, 28S / Q000378:metabolism*; D012867:Skin / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015415:Biomarkers; C507431:KRT16 protein, human; D053536:Keratin-16; D008565:Membrane Proteins; C098069:PIGF protein, human; D012339:RNA, Ribosomal, 28S; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D039942:Neuropilin-1; D040301:Vascular Endothelial Growth Factor Receptor-2