Published in:

Open Access 11-04-2024 | Hypertension | Inflammation and Cardiovascular Diseases (A Kirabo, Section Editor)

Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure

Authors: Maria Balhara, Kit Neikirk, Andrea Marshall, Antentor Hinton Jr., Annet Kirabo

Published in: Current Hypertension Reports | Issue 6/2024

Abstract

Purpose of Review

Hypertension is a principal risk factor for cardiovascular morbidity and mortality, with its severity exacerbated by high sodium intake, particularly in individuals with salt-sensitive blood pressure. However, the mechanisms underlying hypertension and salt sensitivity are only partly understood. Herein, we review potential interactions in hypertension pathophysiology involving the immune system, endoplasmic reticulum (ER) stress, the unfolded protein response (UPR), and proteostasis pathways; identify knowledge gaps; and discuss future directions.

Recent Findings

Recent advancements by our research group and others reveal interactions within and between adaptive and innate immune responses in hypertension pathophysiology. The salt-immune-hypertension axis is further supported by the discovery of the role of dendritic cells in hypertension, marked by isolevuglandin (IsoLG) formation. Alongside these broadened understandings of immune-mediated salt sensitivity, the contributions of T cells to hypertension have been recently challenged by groups whose findings did not support increased resistance of Rag-1-deficient mice to Ang II infusion. Hypertension has also been linked to ER stress and the UPR. Notably, a holistic approach is needed because the UPR engages in crosstalk with autophagy, the ubiquitin proteasome, and other proteostasis pathways, that may all involve hypertension.

Summary

There is a critical need for studies to establish cause and effect relationships between ER stress and the UPR in hypertension pathophysiology in humans and to determine whether the immune system and ER stress function mainly to exacerbate or initiate hypertension and target organ injury. This review of recent studies proposes new avenues for future research for targeted therapeutic interventions.

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Title: Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure
Authors: Maria Balhara
Kit Neikirk
Andrea Marshall
Antentor Hinton Jr.
Annet Kirabo
Publication date: 11-04-2024
Publisher: Springer US
Keywords: Hypertension
Hypertension
Published in: Current Hypertension Reports / Issue 6/2024
Print ISSN: 1522-6417
Electronic ISSN: 1534-3111
DOI: https://doi.org/10.1007/s11906-024-01300-9

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Endoplasmic Reticulum Stress in Hypertension and Salt Sensitivity of Blood Pressure

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