Vascular disease in scleroderma: Angiogenesis and vascular repair

The healing of the ongoing tissue injury that is a hallmark of scleroderma requires generation of new vasculature, mostly at the capillary level. Typically, wound healing is accompanied by extensive angiogenesis driven by vascular endothelial growth factor (VEGF) produced by injured tissues and invading inflammatory cells [1]. The situation in scleroderma is not different; indeed, analysis of skin biopsies from affected and even unaffected areas in patients who have systemic sclerosis (SSc) is consistent with a pro-inflammatory state and increased VEGF production [2-4]. In addition to pro-anglogenic factors, anti-angiogenic factors also have a role in vascular regeneration. Currently, most naturally occurring angiogenic factors are thought to be products of breakdown of the extracellular matrix and other circulating proteins. Endostatin is a cleavage product of collagen XVIII, whereas angiostatin is a product of plasminogen cleavage. Other extracellular matrix-derived inhibitors include tumstatin and canstatin among others (Table 1). Recent evidence suggests that the presence of anti-angiogenic factors in patients with scleroderma may be an important element in the abnormal vascular regeneration seen in this disease [5].