Figure 1.

Vicious circle of hypoxia and fibrosis in the pathogenesis of SSc. To the upper left is shown nailfold capillaroscopy from a patient with systemic sclerosis (SSc) with capillary rarification and vascular alterations, including sac-like, giant and bushy capillaries. Vasculopathy leads to reduced blood flow and causes tissue hypoxia in SSc. To the upper right is shown a haematoxylin and eosin stained skin section from an experimental mouse fibrosis model with increased skin thickness due to extracellular matrix (ECM) deposition. ECM deposition increases diffusion distances from blood vessels to cells and reduces tissue oxygenation. In the 'vicious circle', shown at the bottom of the figure, tissue hypoxia leads to activation of dermal fibroblasts and upregulation of ECM production. Further ECM deposition aggravates tissue malnutrition and hypoxia. Hypoxia once again stimulates ECM production in dermal fibroblasts.