This article appears in the following Rheumatology issue: Update in systemic sclerosis [View the issue table of contents]
Mechanisms of vascular damage in SSc—implications for vascular treatment strategies
1Division of Rheumatology, Department of BioMedicine, AOUC Florence, Florence, Italy, 2Department of Rheumatology, Center of Experimental Rheumatology, University Hospital Zurich, Zurich, Switzerland and 3Department of Rheumatology and Institute for Clinical Immunology, University of Erlangen-Nuremberg, Nuremberg, Germany.
Correspondence to: S. Guiducci, Department of BioMedicine, Division of Rheumatology, AOUC Florence, Italy Viale Pieraccini 1850139 Florence, Italy. E-mail: serena16{at}libero.it
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Abstract |
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Vascular abnormalities are a major component of SSc, but little is known about the events or mechanisms that initiate vascular injury and prevent its repair. In SSc, angiogenesis is incomplete or lacking despite the increased expression of a large array of pro-angiogenic factors such as VEGF. Conflicting results have recently been published concerning the presence and role of vasculogenesis and circulating endothelial progenitor cells in SSc. It remains to be established if these endothelial progenitor cells are a marker of endothelial disease or a cause of insufficient vascular repair. Human mesenchymal stem cells (MSCs) may be an alternative source for endothelial progenitor cells, and it has been observed that the angiogenic potential of endothelial-like MSCs is reduced. Other mechanisms of vascular damage include oxidative stress and factors released from activated platelets. In addition, growth factors such as ET-1 and PDGF induce proliferation of vascular smooth muscle cells resulting in intimal thickening. For the development of new therapeutic strategies, it is important to realize that the different vascular pathologies—uncompensated loss of capillaries on one hand and vascular remodelling with a proliferative vasculopathy on the other—might require different treatment approaches.
KEY WORDS: Systemic sclerosis, Vascular damage, Vascular treatment, Endothelial progenitor cell, Mesenchymal stem cell, Endothelial cell, Angiogenesis, Vasculogenesis, Oxidative stress, Platelet activation
Submitted 1 May 2008; Accepted 18 June 2008