Sirtuin-1 in Hypertension: Linking Oxidative Stress and Mitochondrial Dysfunction to Vascular Aging and Therapeutic Potential

The science

Original title

Sirtuin-1 in Hypertension: Linking Oxidative Stress and Mitochondrial Dysfunction to Vascular Aging and Therapeutic Potential.

Authors

Budziak S, Kloza M, Baranowski P et al.

Journal

Antioxidants (Basel, Switzerland)

Published

Oct 27, 2026

Study type

Review

PMID

42939927 ↗

DOI

10.3390/antiox15101353 ↗

Abstract

Hypertension is a multifactorial cardiovascular disorder characterized by oxidative stress, endothelial dysfunction, chronic inflammation, mitochondrial impairment, and accelerated vascular aging, all of which contribute to hypertension-mediated target organ damage. Among the molecular pathways involved in these processes, sirtuin-1 (SIRT1), a nicotinamide adenine dinucleotide (NAD+)-dependent deacetylase, has emerged as a potential regulator of vascular and metabolic homeostasis. This review summarizes current evidence on the role of SIRT1 in the pathophysiology of hypertension, with particular emphasis on its interactions with oxidative stress, mitochondrial function, endothelial integrity, inflammation, fibrosis, and cellular senescence. Experimental studies suggest that SIRT1 modulation can improve endothelial function and mitochondrial homeostasis, attenuate oxidative stress, inflammation, and vascular remodeling, and limit organ damage in several models. Effects on blood pressure are less consistent and appear to depend on the model and intervention used. Although clinical evidence remains limited, altered SIRT1 expression or activity has been reported in association with hypertension and preeclampsia, while preliminary studies suggest that interventions proposed to activate SIRT1 may improve vascular function and inflammatory status. However, changes in SIRT1 expression might not necessarily reflect changes in its enzymatic activity, and the effects of pharmacological interventions cannot always be attributed specifically to SIRT1. Overall, SIRT1 represents a potential therapeutic target whose value as a biomarker remains uncertain; however, well-designed clinical studies are required to establish its prognostic value and determine whether SIRT1 modulation can improve long-term cardiovascular outcomes.

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