Degradation of Glycocalyx and Multiple Manifestations of Endothelial Dysfunction Coincide in the Early Phase of Endothelial Dysfunction Before Atherosclerotic Plaque Development in Apolipoprotein E/Low‐Density Lipoprotein Receptor‐Deficient Mice

Anna Bar , Marta Targosz-Korecka , Joanna Suraj , Bartosz Proniewski , Agnieszka Jasztal , Brygida Marczyk , Magdalena Sternak , Magdalena Przybyło , Anna Krupińska , Maria Walczak , Renata Kostogrys , Marek Szymonski , Stefan Chlopicki

Abstract

Background: The impairment of endothelium‐dependent vasodilation, increased endothelial permeability, and glycocalyx degradation are all important pathophysiological components of endothelial dysfunction. However, it is still not clear whether in atherosclerosis, glycocalyx injury precedes other features of endothelial dysfunction or these events coincide. Methods and Results: Herein, we demonstrate that in 4‐ to 8‐week‐old apolipoprotein E/low‐density lipoprotein receptor‐deficient mice, at the stage before development of atherosclerotic plaques, impaired acetylcholine‐induced vasodilation, reduced NO production in aorta, and increased endothelial permeability were all observed; however, flow‐mediated dilation in the femoral artery was fully preserved. In 4‐week‐old mice, glycocalyx coverage was reduced and endothelial stiffness was increased, whereas glycocalyx length was significantly decreased at 8 weeks of age. Early changes in endothelial function were also featured by increased plasma concentration of biomarkers of glycocalyx disruption (endocan), biomarkers of endothelial inflammation (soluble vascular cell adhesion molecule 1), increased vascular permeability (angiopoietin 2), and alterations in hemostasis (tissue plasminogen activator and plasminogen activator inhibitor 1). In 28‐week‐old mice, at the stage of advanced atherosclerotic plaque development, impaired NO production and nearly all other features of endothelial dysfunction were changed to a similar extent, compared with the preatherosclerotic plaque phase. The exceptions were the occurrence of acetylcholine‐induced vasoconstriction in the aorta and brachiocephalic artery, impaired flow‐mediated vasodilation in the femoral artery, and further reduction of glycocalyx length and coverage with a concomitant further increase in endothelial permeability. Conclusions: In conclusion, even at the early stage before the development of atherosclerotic plaques, endothelial dysfunction is a complex multifactorial response that has not been previously appreciated.
Author Anna Bar
Anna Bar,,
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, Marta Targosz-Korecka
Marta Targosz-Korecka,,
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, Joanna Suraj
Joanna Suraj,,
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, Bartosz Proniewski
Bartosz Proniewski,,
-
, Agnieszka Jasztal
Agnieszka Jasztal,,
-
, Brygida Marczyk
Brygida Marczyk,,
-
, Magdalena Sternak
Magdalena Sternak,,
-
, Magdalena Przybyło
Magdalena Przybyło,,
-
, Anna Krupińska
Anna Krupińska,,
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, Maria Walczak
Maria Walczak,,
-
et al.`
Journal seriesJournal of the American Heart Association, ISSN 2047-9980, (N/A 140 pkt)
Issue year2019
Vol8
No6
Pages1-18
Publication size in sheets0.85
Article numbere011171
Keywords in Englishatherosclerosis, atomic force microscopy, endothelial function, glycocalyx, magnetic resonance imaging
ASJC Classification2705 Cardiology and Cardiovascular Medicine
DOIDOI:10.1161/JAHA.118.011171
URL https://www.ahajournals.org/doi/full/10.1161/JAHA.118.011171
Internal identifierWTŻ/2019/32
Languageen angielski
LicenseJournal (articles only); author's original; Uznanie Autorstwa (CC-BY); after publication
Score (nominal)140
Score sourcejournalList
Publication indicators WoS Citations = 3; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 1.485; WoS Impact Factor: 2018 = 4.66 (2) - 2018=5.121 (5)
Citation count*
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FinansowanieThis project was financed by the National Science Centre, SYMFONIA Grant DEC‐2015/16/W/NZ4/00070, PRELUDIUM Grant DEC‐2016/23/N/NZ5/00595, and the Foundation for Polish Science from the resources of the TEAM TECH–Core Facility program (application 0016), financed by the European Regional Development Fund under the Intelligent Development Operational Program 2014‐2020 (OP IR), Axis IV, Increasing the scientific and research potential, 4.4: Increasing the human resources potential of the R & D sector.
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
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