Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis

Pier Andrea Nicolosi, Enrico Tombetti, Norma Maugeri, Patrizia Rovere-Querini, Silvia Brunelli, Angelo A. Manfredi

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Fibrosis of the skin and of internal organs, autoimmunity, and vascular inflammation are hallmarks of Systemic Sclerosis (SSc). The injury and activation of endothelial cells, with hyperplasia of the intima and eventual obliteration of the vascular lumen, are early features of SSc. Reduced capillary blood flow coupled with deficient angiogenesis leads to chronic hypoxia and tissue ischemia, enforcing a positive feed-forward loop sustaining vascular remodelling, further exacerbated by extracellular matrix accumulation due to fibrosis. Despite numerous developments and a growing number of controlled clinical trials no treatment has been shown so far to alter SSc natural history, outlining the need of further investigation in the molecular pathways involved in the pathogenesis of the disease. We review some processes potentially involved in SSc vasculopathy, with attention to the possible effect of sustained vascular inflammation on the plasticity of vascular cells. Specifically we focus on mesenchymal transition, a key phenomenon in the cardiac and vascular development as well as in the remodelling of injured vessels. Recent work supports the role of transforming growth factor-beta, Wnt, and Notch signaling in these processes. Importantly, endothelial-mesenchymal transition may be reversible, possibly offering novel cues for treatment.

Original languageEnglish
Article number4636859
JournalStem Cells International
Volume2016
DOIs
Publication statusPublished - 2016

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Systemic Scleroderma
Blood Vessels
Fibrosis
Inflammation
Controlled Clinical Trials
Natural History
Autoimmunity
Transforming Growth Factor beta
Hyperplasia
Cues
Extracellular Matrix
Ischemia
Endothelial Cells
Vascular Remodeling
Skin
Wounds and Injuries
Therapeutics

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis. / Nicolosi, Pier Andrea; Tombetti, Enrico; Maugeri, Norma; Rovere-Querini, Patrizia; Brunelli, Silvia; Manfredi, Angelo A.

In: Stem Cells International, Vol. 2016, 4636859, 2016.

Research output: Contribution to journalArticle

Nicolosi, Pier Andrea ; Tombetti, Enrico ; Maugeri, Norma ; Rovere-Querini, Patrizia ; Brunelli, Silvia ; Manfredi, Angelo A. / Vascular Remodelling and Mesenchymal Transition in Systemic Sclerosis. In: Stem Cells International. 2016 ; Vol. 2016.
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