title: Cellular players in angiogenesis during the course of systemic sclerosis.
abstract: Vascular endothelial injury in Systemic Sclerosis (SSc) leads to pathological changes in the blood vessels that adversely impact the physiology of many organs, resulting in chronic tissue ischemia. The response to hypoxia induces complex cellular and molecular mechanisms in the attempt to recover endothelial cell function and tissue perfusion. The progressive losses of capillaries on one hand, and the vascular remodeling of arteriolar vessels on the other, result in insufficient blood flow, causing severe and chronic hypoxia. Hypoxia is a major stimulus of angiogenesis, leading to the expression of pro-angiogenic molecules, mainly of Vascular Endothelial Growth Factor (VEGF), which triggers the angiogenic process. Nevertheless, in SSc patients there is no evidence of adaptive angiogenesis. Failure of the angiogenic process in SSc largely depends on alteration in the balance between pro- and anti-angiogenic factors, as well as on functional alterations of the cellular players involved in the angiogenic and vasculogenic program. A decreased urokinase plasminogen activator (uPA) dependent invasion, proliferation, and capillary morphogenesis, was showed in SSc endothelial cells (EC). Although hematopoietic endothelial progenitor cells (EPC) count in the peripheral blood of SSc patients is still a matter of controversy, alterations in mobilization process, an excessive immune-mediated EPC destruction in the peripheral circulation or in the bone marrow, a progressive depletion of EPCs following homing to ischemic tissues under persistent peripheral vascular injury, an intrinsic functional impairment could lead to poor vasculogenesis. Human mesenchymal stem cells represent an alternative source of endothelial progenitor cells and it has been observed that their angiogenic potential is reduced in SSc. Targeting autologous stem and progenitor cells could be an ideal tool to counteract and repair dysfunctional angiogenesis.
authors.affiliation: Rheumatology, Department of Internal Medicine and Public Health, University of L'Aquila, Italy. paola.cipriani@cc.univaq.it
authors.forename: Paola
authors.initials: P
authors.lastname: Cipriani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marrelli
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Liakouli
authors.forename: Paola
authors.initials: P
authors.lastname: Di Benedetto
authors.forename: Roberto
authors.initials: R
authors.lastname: Giacomelli
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic; D012595:Scleroderma, Systemic / Q000473:pathology* / Q000503:physiopathology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A