Differential expression of alpha-smooth muscle actin and vascular endothelial growth factor in skin biopsy of patients with systemic sclerosis: a histological and immunohistochemical study

ABSTRACT

Vasculopathy is a hallmark of systemic sclerosis [SSc]. It contributes to many of its clinical manifestations and precedes fibrosis. The aim of this study was to investigate the expression of alpha-smooth muscle actin [alpha-SMA] in skin biopsy of patients with SSc and correlate it with other manifestations of vasculopathy, including those seen on fundus fluorescein angiography and tissue vascular endothelial growth factor [VEGF] expression. This study included 25 patients with SSc and 10 healthy individuals. Patients underwent full history taking and a clinical examination. All participants underwent fundus fluorescein angiography. Skin biopsy was examined by H and E staining, Mallory triple staining, and immunohistochemical staining for alpha-SMA and VEGF. Histological examination showed loss of dermal papillae, hypovascularity of the dermis, and subepidermal fibrosis. Immunohistochemical staining of the vessel wall in skin biopsy samples showed a statistically highly significant increase in VEGF and a highly significant decrease in alpha-SMA in patients as compared with controls. There was a highly significant positive correlation between VEGF and duration of illness, Raynaud's phenomenon, digital ulcers, disease activity score, and modified Rodnan Skin Score. As regards alpha-SMA, there was a highly significant negative correlation with Raynaud's phenomenon, disease activity score, modified Rodnan Skin Score, and VEGF, whereas there was a significant negative correlation with digital ulcers. The strongest correlation [r] for the duration of illness was found with alpha-SMA, followed by VEGF. alpha-SMA was found to be correlated to different manifestations of vasculopathy in SSc. It was found to be one of the early markers of vasculopathy among the other studied variables. Besides its diagnostic role in SSc vasculopathy, it could play a role in impaired vasculogenesis, making it a potential therapeutic target in the management of SSc