The "myth" of loss of angiogenesis in systemic sclerosis: a pivotal early pathogenetic process or just a late unavoidable event?

Systemic sclerosis is considered a disease dominated by a "loss of angiogenesis", although in its early phases evidence indicates a disturbed angiogenic response only. In fact, microvascular changes are primarily due to endothelial cell injury, triggering downstream significant enlargement of the capillary in an inflammatory environment, followed by capillary rupture (microhemorrhages). Subsequent pro-angiogenic efforts lead to an aberrant angiogenesis and, eventually, to a total loss of vessel repair and regeneration (loss of angiogenesis). This clearly suggests that the pathogenetic process has a steady progression: from an early excessive pro-angiogenesis, to an aberrant microvascular regeneration, then ending with a late loss of angiogenesis. Herein, we suggest the loss of angiogenesis should not be considered as an overall "myth" characterizing systemic sclerosis but as a very late event of the vascular pathogenesis. Future research should be oriented essentially on the earlier phases dominated by excessive pro-angiogenesis and microvascular aberration.