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Rapamycin impairs endothelial cell function in human internal thoracic arteries

Overview of attention for article published in European Journal of Medical Research, June 2015
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Title
Rapamycin impairs endothelial cell function in human internal thoracic arteries
Published in
European Journal of Medical Research, June 2015
DOI 10.1186/s40001-015-0150-4
Pubmed ID
Authors

David C. Reineke, Else Müller-Schweinitzer, Bernhard Winkler, Donatina Kunz, Moritz A. Konerding, Thomas Grussenmeyer, Thierry P. Carrel, Friedrich S. Eckstein, Martin T.R. Grapow

Abstract

Definitive fate of the coronary endothelium after implantation of a drug-eluting stent remains unclear, but evidence has accumulated that treatment with rapamycin-eluting stents impairs endothelial function in human coronary arteries. The aim of our study was to demonstrate this phenomenon on functional, morphological and biochemical level in human internal thoracic arteries (ITA) serving as coronary artery model. After exposure to rapamycin for 20 h, functional activity of ITA rings was investigated using the organ bath technique. Morphological analysis was performed by scanning electron microscopy and evaluated by two independent observers in blinded fashion. For measurement of endothelial nitric oxide synthase (eNOS) release, mammalian target of rapamycin (mTOR) and protein kinase B (PKB) (Akt) activation, Western blotting on human mammary epithelial cells-1 and on ITA homogenates was performed. Comparison of the acetylcholine-induced relaxation revealed a significant concentration-dependent decrease to 66 ± 7 % and 36 ± 7 % (mean ± SEM) after 20-h incubation with 1 and 10 μM rapamycin. Electron microscopic evaluation of the endothelial layer showed no differences between controls and samples exposed to 10 μM rapamycin. Western blots after 20-h incubation with rapamycin (10 nM-1 μM) revealed a significant and concentration-dependent reduction of p (Ser 1177)-eNOS (down to 38 ± 8 %) in human mammary epithelial cells (Hmec)-1. Furthermore, 1 μM rapamycin significantly reduced activation of p (Ser2481)-mTOR (58 ± 11 %), p (Ser2481)-mTOR (23 ± 4 %) and p (Ser473)-Akt (38 ± 6 %) in ITA homogenates leaving Akt protein levels unchanged. The present data suggests that 20-h exposure of ITA rings to rapamycin reduces endothelium-mediated relaxation through down-regulation of Akt-phosphorylation via the mTOR signalling axis within the ITA tissue without injuring the endothelial cell layer.

Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 14 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 14 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 4 29%
Researcher 3 21%
Other 2 14%
Student > Doctoral Student 2 14%
Student > Master 1 7%
Other 1 7%
Unknown 1 7%
Readers by discipline Count As %
Medicine and Dentistry 3 21%
Biochemistry, Genetics and Molecular Biology 2 14%
Agricultural and Biological Sciences 2 14%
Neuroscience 2 14%
Nursing and Health Professions 1 7%
Other 4 29%
Attention Score in Context

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 27 June 2015.
All research outputs
#22,759,452
of 25,374,647 outputs
Outputs from European Journal of Medical Research
#728
of 923 outputs
Outputs of similar age
#237,103
of 278,441 outputs
Outputs of similar age from European Journal of Medical Research
#2
of 4 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one is in the 1st percentile – i.e., 1% of other outputs scored the same or lower than it.
So far Altmetric has tracked 923 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.8. This one is in the 1st percentile – i.e., 1% 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 278,441 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 4 others from the same source and published within six weeks on either side of this one. This one has scored higher than 2 of them.