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. SUBJECTS AND 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). CONCLUSION: 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.
Subject(s)
Homeostasis/physiology , Neovascularization, Physiologic/physiology , Scleroderma, Systemic/etiology , Scleroderma, Systemic/physiopathology , Severity of Illness Index , Adult , Biopsy , Case-Control Studies , Disease Progression , Endostatins/blood , Endostatins/physiology , Female , Humans , Male , Middle Aged , Pulmonary Fibrosis/physiopathology , Respiratory Function Tests , Skin/pathology , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/physiologyABSTRACT
OBJECTIVE: To identify the relation between serum levels of N-terminal pro-brain natriuretic peptide (NT-pro BNP) and severity of systemic sclerosis (SSc). SUBJECT AND METHODS: 25 SSc patients and 25 age- and sex-matched healthy controls were included. Assay of serum NT-pro BNP was done for all patients and controls. Patients were subjected to modified Rodnan skin score (mRss), echocardiography, pulmonary function tests and skin biopsies for histopathological skin thickness score assessment. There was a significant increase in the mean values of serum levels of NT- pro BNP in SSc patients compared to controls (t=11, p<0.001). RESULTS: There was a significant positive correlation between serum levels of NT-pro BNP in SSc patients and mRss, systolic pulmonary artery pressure (sPAP) and histopathological skin thickness score (r=0.93, r=0.92, r=0.92, p<0.001 respectively). There was a significant increase in the mean value of serum levels of NT-pro BNP and sPAP in SSc patients with restrictive pulmonary affection compared to those with normal respiratory function tests (p<0.001). CONCLUSION: NT-pro BNP may be a useful biological marker for assessing the severity of SSc as it has a role in detecting the extent of skin fibrosis, the severity of PAH and the degree of restricted pulmonary involvement in SSc patients.
