title: Dysregulation of angiogenic homeostasis in systemic sclerosis.
abstract: BACKGROUND
  Systemic sclerosis (SSc) is a connective tissue disorder characterized by tissue hypoxia and excessive fibrosis of skin and internal organs.
  
  
  OBJECTIVE
  To evaluate the possible role of angiogenesis imbalance in the pathogenesis of SSc.
  
  
  METHODS
  Twenty-five SSc patients and 20 age- and sex-matched healthy controls were included. Assay of serum vascular endothelial growth factor (VEGF) and endostatin was done for all patients and controls using enzyme-linked immunosorbent assay. Patients were subjected to modified Rodnan skin score (mRss), pulmonary function tests (PFTS) and skin biopsies for histopathological skin thickness score assessment.
  
  
  RESULTS
  There was significant increase in the mean levels of serum VEGF and endostatin in SSc patients compared to controls (t = 4.07, P < 0.001). Mean values of serum endostatin was significantly increased in late compared to early stages of disease (t = 6.65, P < 0.01). A significant positive correlation was found between serum levels of endostatin, mRss and histopathological skin thickness score (r = 0.99, 0.94, respectively, P < 0.01). SSc patients with ischemic manifestations had significantly higher levels of serum endostatin compared to those without ischemic manifestations (t = 6.27, P < 0.001). SSc patients with restricted PFTS had significantly higher levels of serum endostatin compared to those without pulmonary manifestations (t = 4.3, P < 0.001).
  
  
  CONCLUSIONS
  Angiogenic inhibitor (endostatin) is induced and outweighs angiogenic inducer (VEGF) in late stages of SSc. Increased serum endostatin is associated with skin sclerosis severity and pulmonary fibrosis and favors SSc disease progression.
authors.affiliation: Department of Internal Medicine and Rheumatology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
authors.forename: Hanan Mohamed
authors.initials: HM
authors.lastname: Farouk
authors.forename: Sherine Hosny
authors.initials: SH
authors.lastname: Hamza
authors.forename: Samah A
authors.initials: SA
authors.lastname: El Bakry
authors.forename: Sahar S
authors.initials: SS
authors.lastname: Youssef
authors.forename: Iman Mohamed
authors.initials: IM
authors.lastname: Aly
authors.forename: Afaf A
authors.initials: AA
authors.lastname: Moustafa
authors.forename: Naglaa Youssef
authors.initials: NY
authors.lastname: Assaf
authors.forename: Al Hussein M
authors.initials: AH
authors.lastname: El Dakrony
mesh_terms: D000328:Adult; D001706:Biopsy; D016022:Case-Control Studies; D018450:Disease Progression; D043169:Endostatins / Q000097:blood / Q000502:physiology; D005260:Female; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011658:Pulmonary Fibrosis / Q000503:physiopathology; D012129:Respiratory Function Tests; D012595:Scleroderma, Systemic / Q000209:etiology* / Q000503:physiopathology*; D012720:Severity of Illness Index; D012867:Skin / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000097:blood / Q000502:physiology
chemical_list: D043169:Endostatins; D042461:Vascular Endothelial Growth Factor A
keywords: angiogenesis; endostatin; skin; systemic sclerosis; vascular endothelial growth factor