Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function

Publication type:
Journal article
Metadata:
Abstract
<jats:p>(1) Background: Endothelial dysfunction initiates cardiovascular pathologies, including peripheral artery disease (PAD). The pathophysiology of impaired new vessel formation in the presence of angiogenic stimuli, such as ischemia and inflammation, is unknown. We have recently shown in mice that reduced endothelial protein C receptor (EPCR) expression results in defective angiogenesis following experimental hindlimb ischemia. (2) Purpose: To determine soluble (s)EPCR levels in the plasma of patients with PAD and to compare them with the protein C activity and biomarkers of endothelial function, inflammation, and angiogenesis. (3) Methods and Results: Clinical tests of vascular function and immunoassays of plasma from patients with PAD stage II were compared to age- and sex-matched individuals with and without cardiovascular risk factors or PAD stage III/IV patients. sEPCR levels were significantly lower in PAD stage II patients compared to subjects with risk factors, but no PAD, and further decreased in PAD stage III/IV patients. Plasma protein C activity or levels of ADAM17, a mediator of EPCR shedding, did not differ. Significant associations between sEPCR and the ankle-brachial index (p = 0.0359), age (p = 0.0488), body mass index (p = 0.0110), and plasma sE-selectin levels (p = 0.0327) were observed. High-sensitive CRP levels and white blood cell counts were significantly elevated in PAD patients and associated with serum glucose levels, but not sEPCR. In contrast, plasma TNFα or IL1β levels did not differ. Circulating levels of VEGF were significantly elevated in PAD stage II patients (p = 0.0198), but not associated with molecular (sE-selectin) or functional (ankle-brachial index) markers of vascular health. (4) Conclusions: Our findings suggest that circulating sEPCR levels may be useful as biomarkers of endothelial dysfunction, including angiogenesis, in persons older than 35 years and that progressive loss of endothelial protein C receptors might be involved in the development and progression of PAD.</jats:p>
Autoren
  • Janina Krug
  • Magdalena L Bochenek
  • Rajinikanth Gogiraju
  • Dagmar Laubert-Reh
  • Karl J Lackner
  • Thomas Münzel
  • Philipp S Wild
  • Christine Espinola-Klein
  • Katrin Schäfer
DOI
10.3390/biomedicines11092459
eISSN
2227-9059
Ausgabe der Veröffentlichung
9
Zeitschrift
Biomedicines
Sprache
en
Online publication date
2023
Paginierung
2459 - 2459
Status
Published online
Herausgeber
MDPI AG
Herausgeber URL
http://dx.doi.org/10.3390/biomedicines11092459
Datum der Datenerfassung
2023
Titel
Circulating Soluble EPCR Levels Are Reduced in Patients with Ischemic Peripheral Artery Disease and Associated with Markers of Endothelial and Vascular Function
Ausgabe der Zeitschrift
11

Data source: Crossref

Other metadata sources:
Author's licence
CC-BY
Autoren
  • Janina Krug
  • Magdalena L Bochenek
  • Rajinikanth Gogiraju
  • Dagmar Laubert-Reh
  • Karl J Lackner
  • Thomas Münzel
  • Philipp S Wild
  • Christine Espinola-Klein
  • Katrin Schäfer
Hosting institution
Universitätsbibliothek Mainz
Sammlungen
  • DFG-491381577-G
Resource version
Published version
DOI
10.3390/biomedicines11092459
Funding acknowledgements
  • Deutsche Forschungsgemeinschaft (DFG)|491381577|Open-Access-Publikationskosten 2022–2024 Universität Mainz - Universitätsmedizin
File(s) embargoed
false
Open access
true
ISSN
2227-9059
Ausgabe der Veröffentlichung
9
Zeitschrift
Biomedicines
Schlüsselwörter
  • 610 Medizin
  • 610 Medical sciences
Sprache
eng
Open access status
Open Access
Paginierung
2459
Datum der Veröffentlichung
2023
Public URL
https://openscience.ub.uni-mainz.de/handle/20.500.12030/10062
Herausgeber
MDPI
Datum der Datenerfassung
2024
Datum, an dem der Datensatz öffentlich gemacht wurde
2024
Zugang
Public
Titel
Circulating soluble EPCR levels are reduced in patients with ischemic peripheral artery disease and associated with markers of endothelial and vascular function
Ausgabe der Zeitschrift
11

Files

circulating_soluble_epcr_leve-20240205163047021.pdf

Data source: OPENSCIENCE.UB

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