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Sirtuin 1 and endothelial glycocalyx

Authors
 Mark Lipphardt  ;  Jong Wook Song  ;  Michael S Goligorsky 
Citation
 PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, Vol.472(8) : 991-1002, 2020-08 
Journal Title
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
ISSN
 0031-6768 
Issue Date
2020-08
MeSH
Animals ; Endothelial Cells / metabolism* ; Endothelium / metabolism* ; Glycocalyx / metabolism* ; Humans ; Nitric Oxide / metabolism ; Sirtuin 1 / metabolism*
Keywords
Glycocalyx ; NF-kB ; Oxidative stress ; Sheddases ; Sirtuin 1 ; Syndecan-4
Abstract
Sirtuin1 deficiency or reduced activity comprises one of the hallmarks of diseases as diverse as chronic cardiovascular, renal, and metabolic, some malignancies, and infections, as well as aging-associated diseases. In a mouse model of endothelium-limited defect in sirtuin 1 deacetylase activity, we found a dramatic reduction in the volume of endothelial glycocalyx. This was associated with the surge in the levels of one of key scaffolding heparan sulfate proteoglycans of endothelial glycocalyx, syndecan-4, and specifically, its extracellular domain (ectodomain). We found that the defect in endothelial sirtuin 1 deacetylase activity is associated with (a) elevated basal and stimulated levels of superoxide generation (via the FoxO1 over-acetylation mechanism) and (b) increased nuclear translocation of NF-kB (via p65 over-acetylation mechanism). These findings laid the foundation for the proposed novel function of sirtuin 1, namely, the maintenance of endothelial glycocalyx, particularly manifest in conditions associated with sirtuin 1 depletion. In the forthcoming review, we summarize the emerging conceptual framework of the enhanced glycocalyx degradation in the states of defective endothelial sirtuin 1 function, thus explaining a broad footprint of the syndrome of endothelial dysfunction, from impaired flow-induced nitric oxide production, deterrent leukocytes infiltration, increased endothelial permeability, coagulation, and pro-inflammatory changes to development of microvascular rarefaction and progression of an underlying disease.
Files in This Item:
T202007192.pdf Download
DOI
10.1007/s00424-020-02407-z
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anesthesiology and Pain Medicine (마취통증의학교실) > 1. Journal Papers
Yonsei Authors
Song, Jong Wook(송종욱) ORCID logo https://orcid.org/0000-0001-7518-2070
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/183876
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