Biomedical Sciences ETDs
Publication Date
Summer 7-28-2026
Abstract
Excess dietary sodium contributes to hypertension and vascular dysfunction, yet preclinical studies rely on inbred C57BL/6 mice, which may not be susceptible to high-sodium (HS) diet-induced cardiovascular dysfunction. Here we evaluated the outbred UM-HET3 mouse as a translational model of sodium-induced cardiovascular dysfunction. A meta-analysis of 39 studies demonstrated marked variability in vascular responses to HS diet in C57BL/6 mice, with most studies reporting no increase in blood pressure. Comparative studies showed that UM-HET3 mice displayed greater vascular function and endothelial glycocalyx (eGX) integrity compared with C57BL/6 substrains. Following HS diet, UM-HET3, but not C57BL/6J, mice developed elevated blood pressure, vascular dysfunction, and eGX depletion. eGX depletion occurred within one week of HS diet and was associated with increased salt-inducible kinase (SIK2/3) expression and reduced hyaluronan synthase-2 (HAS2). Pharmacological SIK inhibition partially prevented eGX depletion and vascular dysfunction, suggesting the SIK-HAS2 axis as a therapeutic target in HS diet.
Keywords
Endothelial glycocalyx, High-sodium Diet, SIK-HAS2 axis, Hyaluronan synthesis
Document Type
Thesis
Language
English
Degree Name
Biomedical Sciences
Level of Degree
Doctoral
Department Name
Biomedical Sciences Graduate Program
First Committee Member (Chair)
Jay Naik
Second Committee Member
Daniel Machin
Third Committee Member
Laura Gonzalez Bosc
Fourth Committee Member
Jing Pu
Recommended Citation
Sabouri, Mostafa. "ROLE OF SALT-INDUCIBLE KINASES IN HIGH-SODIUM DIET-INDUCED ENDOTHELIAL GLYCOCALYX DEPLETION AND VASCULAR DYSFUNCTION." (2026). https://digitalrepository.unm.edu/biom_etds/324