Clinical utility of vascular endothelial growth factor (VEGF)‎ in systemic sclerosis patients

Abstract EN

Objective: To study serum levels and clinical correlation of vascular endothelial growth factor (VEGF) in systemic sclerosis (SSc) patients in order to establish the clinical utility of VEGF as a new prognostic serum marker in SSc.

Study design: Serum samples from 42 SSc patients [20 with limited systemic sclerosis (LSSc) and 22 with diffuse systemic sclerosis (DSSc)] in addition to 20 age and sex-matched healthy controls were analyzed with ELISA for the determination of VEGF levels.

Clinical assessment for patients and controls was done with stress on pulmonary affection with pulmonary function tests.

Histopathological examination of skin biopsy specimens was done for detection of fibrosis and vascular abnormalities.

Results: Serum VEGF levels in SSc patients (362?273 pg/mL) were significantly higher than in controls (119?58 pg/mL) (p<0.01).

DSSc patients showed significantly higher serum VEGF levels (589?243 pg/mL) than LSSc patients (192?94 pg/mL) (p < 0.01).

As for clinical correlation of VEGF, SSc patients with elevated levels of VEGF had pulmonary fibrosis, decreased DLCO, and decreased vital capacity more frequently than those with normal VEGF levels (p < 0.01).

Furthermore, DLCO and vital capacity were inversely correlated with serum VEGF levels in SSc patients (r = -0.49, -0.42, respectively p<0.01).

Stepwise multi-regression analysis revealed that the correlation of VEGF levels with pulmonary fibrosis was the strongest (F = 15, p<0.001).

The DSSc patients with disease duration of 1-3 years had significantly elevated levels of VEGF compared with DSSc patients with duration < 1year or > 3 years (p < 0.05).

The serum levels of VEGF were directly correlated with collagen deposition and fibrosis of endothelial lining of blood vessels in skin biopsy specimens (r = 0.39, p<0.05).

VEGF levels were significantly associated with joint inflammation and rheumatoid factor (RF) (p < 0.01).

Conclusion: Serum VEGF levels were increased in SSc patients, and correlated with the extent of skin sclerosis and the severity of pulmonary fibrosis.

In addition, it appears that the production of VEGF is involved in the development and maintenance of fibrosis rather than in its initiation.

These data suggest that VEGF plays a critical role in the development of fibrosis in SSc and can be used as a prognostic serum marker for SSc.

The fact that VEGF correlated with joint inflammation suggests that anti-angiogenic treatment could represent a novel therapy for rheumatic diseases in the future, particularly molecules targeting VEGF, which requires further work.