Serum vasohibin‐1 levels: A potential marker of dermal and pulmonary fibrosis in systemic sclerosis

Abstract

Vasohibin‐1 (VASH‐1) is a potent anti‐angiogenic factor mainly produced by endothelial cells. In addition, VASH‐1 prevents TGF‐β–dependent activation of renal fibroblasts. Since systemic sclerosis (SSc) is an autoimmune disease characterized by vasculopathy and fibrosis of multiple organs, VASH‐1 may be involved in the development of this disease. In this study, we investigated the potential role of VASH‐1 in SSc by evaluating the clinical correlation between serum VASH‐1 levels and the expression of VASH‐1 in SSc‐involved skin. Serum VASH‐1 levels were higher in SSc patients, especially those with diffuse cutaneous involvement, than in healthy controls and positively correlated with skin score. Furthermore, SSc patients with interstitial lung disease had significantly elevated levels of serum VASH‐1 as compared to those without. Importantly, serum VASH‐1 levels correlated inversely with both the percentage of predicted vital capacity and the percentage of predicted diffusion lung capacity for carbon monoxide and positively with serum KL‐6 levels, but not serum surfactant protein D levels. In SSc‐involved skin, VASH1 mRNA was remarkably upregulated compared with healthy control skin, but the major source of VASH‐1 was not clear. Fli1 deficiency, a predisposing factor inducing SSc‐like endothelial properties, did not affect VASH‐1 expression in human dermal microvascular endothelial cells. Collectively, these results suggest that VASH‐1 upregulation in the skin and sera is linked to dermal and pulmonary fibrotic changes in SSc, while the contribution of VASH‐1 to SSc vasculopathy seems to be limited.

In search of the needle in a haystack: Finding a suitable serum biomarker for monitoring disease activity of systemic sclerosis

“…VASH‐1 immunoreactivity was seen in dermal fibroblasts, endothelial cells, pericytes, vascular smooth muscle cells and some inflammatory cells. Interestingly, the genetic knockdown of Fli1, a transcription linking peripheral vasculopathy with dermal fibrosis in SSc, 116 did not alter endothelial‐derived secretion of VASH‐1 123 …”

“…However, with regard to skin, very little is known about the expression, regulation and function of vasohibins 122 . Fukui et al ., in the current issue, 123 have now set foot on the terra incognita of vasohibins and scleroderma by testing the hypothesis whether VASH‐1 is a biomarker in SSc. They show an association of the serum levels of this antiangiogenic factor for the first time in SSc, relate the detected VASH‐1 in blood to disease activity, type of organ involvement, and to patient´s clinical response to administered therapies.…”

“…They show an association of the serum levels of this antiangiogenic factor for the first time in SSc, relate the detected VASH‐1 in blood to disease activity, type of organ involvement, and to patient´s clinical response to administered therapies. The authors also sought to disclose the source and molecular mechanism of aberrant VASH‐1 production 123 …”

“…Fukui et al . in the current issue 123 explore the potential role of VASH‐1 in SSc by determining the clinical correlation between serum levels of this antiangiogenic factor and its expression in lesional skin with SSc disease activity. The patient cohort included 50 SSc patients and 19 healthy controls.…”

“…Oesophageal involvement was assessed by barium‐contrast radiography and right ventricular systolic pressure (RVSP) by echocardiography. Additional investigations of VASH‐1 in situ expression included quantitative reverse transcription‐polymerase chain reaction (qRT‐PCR) and immunohistochemistry of samples from lesional skin and controls 123 …”