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PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury

Overview of attention for article published in Proceedings of the National Academy of Sciences of the United States of America, January 2018
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • Good Attention Score compared to outputs of the same age and source (78th percentile)

Mentioned by

news
8 news outlets
blogs
2 blogs
twitter
9 tweeters

Citations

dimensions_citation
20 Dimensions

Readers on

mendeley
45 Mendeley
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Title
PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury
Published in
Proceedings of the National Academy of Sciences of the United States of America, January 2018
DOI 10.1073/pnas.1718600115
Pubmed ID
Authors

Karen De Ceunynck, Christian G. Peters, Abhishek Jain, Sarah J. Higgins, Omozuanvbo Aisiku, Jennifer L. Fitch-Tewfik, Sharjeel A. Chaudhry, Chris Dockendorff, Samir M. Parikh, Donald E. Ingber, Robert Flaumenhaft

Abstract

Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB-mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling.

Twitter Demographics

The data shown below were collected from the profiles of 9 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 45 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 45 100%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 9 20%
Researcher 8 18%
Student > Ph. D. Student 6 13%
Student > Master 5 11%
Professor 4 9%
Other 8 18%
Unknown 5 11%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 9 20%
Agricultural and Biological Sciences 7 16%
Medicine and Dentistry 7 16%
Engineering 5 11%
Pharmacology, Toxicology and Pharmaceutical Science 4 9%
Other 5 11%
Unknown 8 18%

Attention Score in Context

This research output has an Altmetric Attention Score of 73. 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 May 2019.
All research outputs
#273,565
of 14,780,221 outputs
Outputs from Proceedings of the National Academy of Sciences of the United States of America
#5,893
of 83,390 outputs
Outputs of similar age
#10,945
of 358,281 outputs
Outputs of similar age from Proceedings of the National Academy of Sciences of the United States of America
#205
of 952 outputs
Altmetric has tracked 14,780,221 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 83,390 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.4. This one has done particularly well, scoring higher than 92% of its peers.
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 358,281 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 952 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 78% of its contemporaries.