Novel Aspects in the Pathophysiology of Peripheral Vasculopathy in Systemic Sclerosis

Systemic sclerosis (SSc) is a multisystem connective tissue disease characterized by fibrosis, autoimmunity and vascular damage. Although fibrosis is often considered the main feature of the disease, there is evidence that the underlying vasculopathy plays an important role in the initiation and perpetuation of SSc. Vascular manifestations such as Raynaud's phenomenon and digital ulcers are prominent in early disease stages and might substantially contribute to the SSc related mortality in later disease stages when pulmonary arterial hypertension becomes clinically evident. Vascular damage is thought to start with endothelial cell injury and apoptosis resulting in tissue hypoxia. Hypoxia is considered a main stimulus for vascular regenerative processes. However, despite the significant deterioration in number and quality of microvessels, there is a lack of appropriate compensatory repair processes by angiogenesis and vasculogenesis. In this review, we will discuss recent data about the pathophysiology of peripheral (acral) microvascular damage in SSc, highlight novel aspects behind the defective repair mechanisms in the vascular system in SSc and focus on SSc animal models with peripheral vascular changes.