Reviews
A new avenue in the pathogenesis of systemic sclerosis: the molecular interface between the endothelial and the nervous systems
E. Romano1, I. Rosa2, B.S. Fioretto3, S. Guiducci4, M. Manetti5, M. Matucci-Cerinic6
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy. eloisaromano@libero.it
- Division of Rheumatology, Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC) and Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Italy.
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy.
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy.
- Section of Anatomy and Histology, Department of Experimental and Clinical Medicine, University of Florence, Italy.
- Division of Rheumatology, Department of Experimental and Clinical Medicine, University of Florence, Scleroderma Unit, Azienda Ospedaliero-Universitaria Careggi (AOUC), Florence, Italy.
CER12010
2019 Vol.37, N°4 ,Suppl.119
PI 0133, PF 0140
Reviews
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PMID: 31025932 [PubMed]
Received: 20/12/2018
Accepted : 11/03/2019
In Press: 11/04/2019
Published: 03/10/2019
Abstract
Systemic sclerosis (SSc) is a connective tissue disorder characterised by immune dysregulation, endothelial cell dysfunction followed by defective vascular repair and neovascularization and progressive tissue fibrosis of the skin and internal organs, whose pathophysiology remains to be fully elucidated. Perturbed neuroendothelial control mechanisms comprising either endothelial cell or peripheral nerve fiber impairment are supposed to play an important role in the onset of Raynaud’s phenomenon and development of microvascular abnormalities which are the earliest events and key features of SSc. Such pathogenic neuroendothelial mechanisms may trigger both the early endothelial cell damage and the subsequent loss of peripheral microvascular integrity characterised by the lack of compensatory angiogenesis. Of note, the vascular and nervous systems have several anatomical similarities that extend to molecular level, and the molecular mechanisms of nerve regulation are shared by the vascular system. In this context, increasing evidence demonstrated that endothelial cells express receptors for axon guidance molecules, including Ephrin family receptor tyrosine kinases, Neuropilins, Plexins, Robos, and UNC5B that are able to respond to their soluble neuroendothelial trophic ligands, such as Semaphorins and Slits, to guide the sprouting of endothelial tip cells. Here, we first provide a historical view of neuroendothelial control mechanism alterations in the pathogenesis of SSc, and then discuss the emerging role of a class of molecules sharing neurogenic and angiogenic properties, such as members of Semaphorin/Plexin/Neuropilin and Slit/Roundabout families, in SSc-related peripheral microvasculopathy.
