NYMC Faculty Publications
Sirtuin 1 and Endothelial Glycocalyx
DOI
10.1007/s00424-020-02407-z
Journal Title
Pflugers Archiv : European Journal of Physiology
First Page
991
Last Page
1002
Document Type
Review Article
Publication Date
8-2020
Department
Medicine
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.
Recommended Citation
Lipphardt, M., Song, J. W., & Goligorsky, M. S. (2020). Sirtuin 1 and Endothelial Glycocalyx. Pflugers Archiv : European Journal of Physiology, 472 (8), 991-1002. https://doi.org/10.1007/s00424-020-02407-z