Endothelial dysfunction in aging associated with reduced Niban phosphorylation

TL;DR

This study shows that reduced Niban phosphorylation in aging contributes to vascular dysfunction and suggests a potential treatment to counteract it.

Contribution

The study identifies Niban phosphorylation as a novel target for treating age-related vascular dysfunction.

Findings

Aged aortas showed reduced Niban phosphorylation and increased MAPK signaling.

NiPp treatment attenuated IL-1β-induced endothelial dysfunction in aged aortas.

Reduced Niban phosphorylation is linked to vascular aging and cardiovascular risk.

Abstract

Cardiovascular diseases are the leading cause of mortality worldwide, with aging and endothelial dysfunction being key contributors to its progression. Age-related vascular dysfunction is characterized by impaired endothelial-dependent relaxation, increased vascular inflammation, and heightened susceptibility to injury, all of which exacerbate cardiovascular risk. The multi-functional protein Niban restores vascular function following injury, with reduced Niban phosphorylation linked to activation of mitogen-activated protein kinase (MAPK) pathways. We hypothesized that reduced Niban phosphorylation and increased inflammatory MAPK signaling would be associated with vascular dysfunction in aging that can be attenuated by NiPp, a cell permeant phosphomimetic peptide of Niban.

Aortas from young (3-months-old, N = 8) and aged (20- to 23-month-old N = 8) rats were assessed for vascular reactivity as well as protein levels and protein phosphorylation. Aged aortas displayed impaired contractility, endothelial-dependent relaxation, reduced phosphorylated Niban levels, and increased phosphorylation of inflammatory MAPK pathway elements including c-Jun N-terminal kinase, MAP kinase-activated protein kinase 2, phosphorylated cAMP response element-binding protein, and downstream vascular cell adhesion molecule-1. Aged aortas also exhibited greater IL-1β-induced loss of endothelial-dependent relaxation ex vivo, which was attenuated by NiPp treatment.

These results identify reduced Niban phosphorylation and increased MAPK signaling as contributors to age-related endothelial dysfunction and highlight Niban phosphorylation as a possible target for treating vascular aging and associated cardiovascular diseases.

The online version contains supplementary material available at 10.1007/s11033-026-11504-8.

Figures