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Dysregulation of angiogenic homeostasis in systemic sclerosis
Author(s) -
Farouk Hanan Mohamed,
Hamza Sherine Hosny,
El Bakry Samah A.,
Youssef Sahar S.,
Aly Iman Mohamed,
Moustafa Afaf A.,
Assaf Naglaa Youssef,
El Dakrony Al Hussein M.
Publication year - 2013
Publication title -
international journal of rheumatic diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.795
H-Index - 41
eISSN - 1756-185X
pISSN - 1756-1841
DOI - 10.1111/1756-185x.12130
Subject(s) - endostatin , medicine , angiogenesis , pathogenesis , vascular endothelial growth factor , gastroenterology , fibrosis , pathology , pulmonary function testing , connective tissue disease , connective tissue , vegf receptors , disease , autoimmune disease
Abstract Background Systemic sclerosis ( SS c) 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 SS c. Subjects and methods Twenty‐five SS c 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 ( mR ss), 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, mR ss 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). Conclusion Angiogenic inhibitor (endostatin) is induced and outweighs angiogenic inducer ( VEGF ) in late stages of SS c. Increased serum endostatin is associated with skin sclerosis severity and pulmonary fibrosis and favors SS c disease progression.