# Altered Plasma Membrane Lipid Composition in Hypertensive Neutrophils Impacts Epithelial Sodium Channel (ENaC) Endocytosis

## TL;DR

This study shows that changes in the lipid composition of neutrophil membranes in hypertensive patients affect how a sodium channel called ENaC is removed from the cell surface.

## Contribution

The study reveals novel lipid and kinase-related mechanisms affecting ENaC endocytosis in hypertension.

## Key findings

- Neutrophils from hypertensive patients show altered plasma membrane lipid composition.
- Altered microdomains and SGK1 kinase activity may prolong ENaC presence on the membrane.
- Proteasomal and lysosomal pathways are less effective in removing ENaC in hypertension.

## Abstract

Biological membranes are composed of a lipid bilayer with embedded proteins, including ion channels like the epithelial sodium channel (ENaC), which are critical for sodium homeostasis and implicated in arterial hypertension (HTN). Changes in the lipid composition of the plasma membrane can significantly impact cellular processes related to physiological functions. We hypothesized that the observed overexpression of ENaC in neutrophils from HTN patients might result from alterations in the structuring domains within the plasma membrane, disrupting the endocytic processes responsible for ENaC retrieval. This study assessed the structural lipid composition of neutrophil plasma membranes from HTN patients along with the expression patterns of key elements regulating ENaC at the plasma membrane. Our findings suggest alterations in microdomain structure and SGK1 kinase activity, which could prolong ENaC presence on the plasma membrane. Additionally, we propose that the proteasomal and lysosomal degradation pathways are insufficient to diminish ENaC presence at the plasma membrane in HTN. These results highlight the importance of understanding ENaC retrieval mechanisms and suggest that targeting these mechanisms could provide insights for developing drugs to prevent and treat HTN.