title: Vascular endothelial growth factor (VEGF)-A and platelet-derived growth factor (PDGF) play a central role in the pathogenesis of digital clubbing.
abstract: Digital clubbing is associated with many unrelated serious diseases but its pathogenesis remains a clinical enigma. It has been hypothesized that platelet clusters impacting in the distal vasculature mediate the morphological changes of clubbing. Since the multifunctional cytokines vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) are released on platelet aggregation and are hypoxically regulated, the present study has examined their role in clubbing using immunohistochemistry. Basic fibroblast growth factor (bFGF), transforming growth factor-beta 1 (TGF-beta1), microvessel density, carbonic anhydrase IX (CAIX), hypoxia inducible factor (HIF)-1alpha, and HIF-2alpha were also measured. There was a significant increase in VEGF (p = 0.01), pKDR (p = 0.03), PDGF (p = 0.017), and HIF-1alpha and HIF-2alpha (p = 0.004 and p = 0.004, respectively) expression together with a significant increase in microvessel density (p = 0.03) in the stroma in clubbed digits compared with controls. There was no difference in CAIX (p = 0.25), TGF-beta1 (p = 0.66) or bFGF (p = 0.18) between affected and control groups. These findings suggest that VEGF and PDGF are released after platelet impaction and that their expression is hypoxically enhanced in the stroma after capillary occlusion. VEGF may synergize with PDGF in inducing the stromal and vascular changes present in digital clubbing.
authors.affiliation: Nuffield Department of Clinical Laboratory Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK.
authors.forename: Stephen
authors.initials: S
authors.lastname: Atkinson
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Fox
mesh_terms: D000951:Antigens, Neoplasm / Q000032:analysis; D001160:Arterioles; D002196:Capillaries; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000032:analysis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D005385:Fingers / Q000098:blood supply* / Q000473:pathology; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007150:Immunohistochemistry / Q000379:methods; D009389:Neovascularization, Pathologic / Q000473:pathology / Q000503:physiopathology; D010005:Osteoarthropathy, Secondary Hypertrophic / Q000473:pathology / Q000503:physiopathology*; D010974:Platelet Aggregation / Q000502:physiology; D010982:Platelet-Derived Growth Factor / Q000502:physiology*; D040262:Receptors, Vascular Endothelial Growth Factor / Q000032:analysis; D014157:Transcription Factors / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000032:analysis; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
chemical_list: D000951:Antigens, Neoplasm; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010982:Platelet-Derived Growth Factor; C508960:TGFB1 protein, human; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D040262:Receptors, Vascular Endothelial Growth Factor; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases