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Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study

Overview of attention for article published in Arthritis Research & Therapy, October 2016
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Title
Bosentan and macitentan prevent the endothelial-to-mesenchymal transition (EndoMT) in systemic sclerosis: in vitro study
Published in
Arthritis Research & Therapy, October 2016
DOI 10.1186/s13075-016-1122-y
Pubmed ID
Authors

Claudio Corallo, Maurizio Cutolo, Bashar Kahaleh, Gianluca Pecetti, Antonio Montella, Chiara Chirico, Stefano Soldano, Ranuccio Nuti, Nicola Giordano

Abstract

Systemic sclerosis (SSc) is characterized by early vascular abnormalities and subsequent fibroblast activation to myofibroblasts, leading to fibrosis. Recently, endothelial-to-mesenchymal transition (EndoMT), a complex biological process in which endothelial cells lose their specific markers and acquire a mesenchymal or myofibroblastic phenotype, has been reported in SSc. In the present study, we evaluated the ability of endothelin-1 (ET-1) dual receptor antagonists bosentan (BOS) and macitentan (MAC) to antagonize EndoMT in vitro. Ten women with limited SSc were enrolled. They underwent double skin biopsy (affected and nonaffected skin). Fibroblasts and microvascular endothelial cells (MVECs) were isolated from biopsies. We performed mono- or coculture of MVECs (isolated from nonaffected skin) with fibroblasts (isolated from affected skin and stimulated with ET-1 and transforming growth factor beta [TGF-β]). In cocultures, the MVEC layer was left undisturbed or was preincubated with BOS or MAC. After 48 h of coculture, MVECs were analyzed for their tube formation ability and for messenger RNA and protein expression of different vascular (CD31, vascular endothelial growth factor-A [VEGF-A], VEGF-A165b) and profibrotic (alpha-smooth muscle actin [α-SMA], collagen type I [Col I], TGF-β) molecules. After 48 h, MVECs showed a reduced tube formation ability when cocultured with SSc fibroblasts. CD31 and VEGF-A resulted in downregulation, while VEGF-A165b, the antiangiogenic isoform, resulted in upregulation. At the same time, mesenchymal markers α-SMA, Col I, and TGF-β resulted in overexpression in MVECs. Tube formation ability was restored when MVECs were preincubated with BOS or MAC, also reducing the expression of mesenchymal markers and restoring CD31 expression and the imbalance between VEGF-A and VEGF-A165b. With this innovative EndoMT in vitro model realized by coculturing nonaffected MVECs with affected SSc fibroblasts, we show that the presence of a myofibroblast phenotype in the fibroblast layer, coupled with an ET-1-TGF-β synergic effect, is responsible for EndoMT. BOS and MAC seem able to antagonize this phenomenon in vitro, confirming previous evidence of endothelium-derived fibrosis in SSc and possible pharmacological interference.

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 5 29%
Researcher 3 18%
Student > Master 2 12%
Other 1 6%
Student > Doctoral Student 1 6%
Other 1 6%
Unknown 4 24%
Readers by discipline Count As %
Medicine and Dentistry 5 29%
Biochemistry, Genetics and Molecular Biology 4 24%
Agricultural and Biological Sciences 2 12%
Unknown 6 35%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 02 November 2016.
All research outputs
#7,238,222
of 11,622,318 outputs
Outputs from Arthritis Research & Therapy
#1,191
of 1,602 outputs
Outputs of similar age
#143,876
of 257,201 outputs
Outputs of similar age from Arthritis Research & Therapy
#20
of 32 outputs
Altmetric has tracked 11,622,318 research outputs across all sources so far. This one is in the 23rd percentile – i.e., 23% of other outputs scored the same or lower than it.
So far Altmetric has tracked 1,602 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 5.5. This one is in the 23rd percentile – i.e., 23% of its peers scored the same or lower than it.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 257,201 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 34th percentile – i.e., 34% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 32 others from the same source and published within six weeks on either side of this one. This one is in the 25th percentile – i.e., 25% of its contemporaries scored the same or lower than it.