Molecular mechanisms of cardiovascular complications in kidney disease

Date
2023
DOI
Authors
Seabra, Pedro Maria
Version
Embargo Date
2026-03-08
OA Version
Citation
Abstract
BACKGROUND: Chronic kidney disease (CKD) and cardiovascular disease (CVD) are diseases with the highest mortality worldwide. The molecular mechanisms that relate CKD with CVD have not yet been fully elucidated; both conditions have increased exponentially over the last few decades. MINAR1, a novel protein that activates the Notch2 signaling pathway and inhibits angiogenesis, has been shown to increase in the AV fistulas of CKD patients. Objectives: To determine the role of MINAR1 in the vasculature of both WT and MINAR1KO mice. Determine expression levels of MINAR1 in murine and human VSMC and whether uremic solutes, which are elevated in CKD patients, affect MINAR1 level of expression; lastly, we sought to establish whether the effects of MINAR1 on VSMC are mediated by Notch signaling. METHODS: WT and MINAR1KO mice received either normal (control) or adenine-rich diets to induce CKD, and PWV, an index of arterial stiffness, was measured. Murine and human VSMC were treated with different types and concentration of uremic solutes and levels of MINAR1 and Notch2 were measured through western blotting. RESULTS: In MINAR1KO mice, AD induced a greater increase in PWV compared to control diet than in WT mice. MINAR1 decreased in response to Indoxyl Sulfate (IS) in murine VSMC but it increased in human VSMC. In both murine and human VSMC, active Notch2 correlated with MINAR1 levels. CONCLUSION: MINAR1 is expressed in VSMCs and it could affect the vascular function of CKD patients via activation of the Notch2 signaling pathway.
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