Evidence map›Paper›PMID 41723507›Full record

ArticleBiology of sex differences2026

Sex-specific hypothalamic PVN transcriptomic signatures of blood pressure autonomic regulation and neuroinflammation in hypertension.

V J Duque, J V Nani, M Jovanovic, M Lozić, O Šarenac, A G Pauža, D M Murphy, N Z Japundžić-Žigon, A S Mecawi

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Article in Biology of sex differences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

V J DuqueLaboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
J V NaniLaboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil.
M JovanovicDepartment of Pathophysiology, University of Belgrade Faculty of Medicine, Belgrade, RS, Serbia.
M LozićDepartment of Pharmacology, University of Belgrade Faculty of Medicine, Belgrade, RS, Serbia.
O ŠarenacDepartment of Pharmacology, University of Belgrade Faculty of Medicine, Belgrade, RS, Serbia.
A G PaužaMolecular Neuroendocrinology Research Group, Bristol Medical School: Translational Health Sciences, Dorothy Hodgkin Building, University of Bristol, Bristol, UK.
D M MurphyMolecular Neuroendocrinology Research Group, Bristol Medical School: Translational Health Sciences, Dorothy Hodgkin Building, University of Bristol, Bristol, UK.
N Z Japundžić-Žigon *Department of Pharmacology, University of Belgrade Faculty of Medicine, Belgrade, RS, Serbia. nina.zigon@med.bg.ac.rs.
A S Mecawi *Laboratory of Molecular Neuroendocrinology, Department of Biophysics, Paulista School of Medicine, Federal University of São Paulo, São Paulo, Brazil. mecawi@unifesp.br.

Funding

Biotechnology and Biological Sciences Research Council BB/R016879/1Conselho Nacional de Desenvolvimento Científico e Tecnológico 421434/2023-6 and 402719/2022-0Coordenação de Aperfeiçoamento de Pessoal de Nível Superior Finance Code 001Fundação de Amparo à Pesquisa do Estado de São Paulo 2019/27581-0, 2024/01620-7 and 2024/19300-9Fundação de Amparo à Pesquisa do Estado de São Paulo 2021/14426-6Fundação de Amparo à Pesquisa do Estado de São Paulo 2024/15733-8Medical Research Council MR/W028999/1 and MR/N022807/1Ministry of Science, Technological Development and Innovation of Serbia 451-03-137/2025-03/200110
6 · The paper itself

Abstract

introductionHypertension is a multifactorial condition of unknown cause that affects more than 1.28 billion adults worldwide and impacts the sexes differently. The hypothalamic paraventricular nucleus (PVN) plays a central role in blood pressure (BP) regulation by modulating sympathetic tone and releasing neuropeptides that affect the cardiovascular function. In this study, we investigated the transcriptomic profile of the PVN in hypertensive strains and across sexes, aiming to identify novel sex-specific molecular pathways involved in the regulation of BP.

methodsTo accomplish this goal, we sequenced RNA from the PVNs of normotensive Wistar rats and Spontaneously Hypertensive Rats (SHR), both male and female. We also performed a cardiovascular assessment based on blood pressure (BP) measurements and their variability.

resultsCardiovascular assessment revealed higher SBP in SHRs than in Wistar rats; while males exhibited greater autonomic regulation associated with vasomotor and neurohumoral mechanisms, while females maintained comparable SBP levels primarily through an increase in heart rate, reflecting distinct autonomic adaptations. Hypertension also impacted gene expression, with influences from both the hypertensive state and sex. Compared with female SHRs, male SHRs presented a marked increase in differentially expressed genes (DEGs). Key upregulated genes in males, including Brain-Derived Neurotrophic Factor (Bdnf) and Hypocretin (Hcrt), have already been linked to elevated BP, and Angiotensin II Receptor Type 1 (Agtr1a) is possibly associated with increased SBP-VLF variability, which serves as an indirect measure of enhanced sympathetic tone. In contrast, the female transcriptomic signature was characterized by the upregulation of anti-inflammatory pathways, with upregulation of NLR Family CARD Domain Containing 3 (Nlrc3) and Paired Ig-like Receptor B (Pirb), and downregulation of Absent in Melanoma 2 (Aim2), and S100 Calcium Binding Protein B (S100b). Notably, genes associated with neuroinflammation, such as the downregulation of Annexin A1 (Anxa1) and the upregulation of Solute Carrier Family 11 Member 1 (Slc11a1), were consistently altered in both sexes.

conclusionThese results provide new insights into the cardiovascular and molecular basis of sex differences in hypertension, suggesting distinct neurohumoral autonomic profile in males, whereas in females a greater anti-inflammatory component. These findings offer a valuable framework for developing future sex-specific therapeutic strategies.

Indexed as

Autonomic Nervous SystemBlood PressureHypertensionNeuroinflammatory DiseasesParaventricular Hypothalamic NucleusSex CharacteristicsTranscriptomeAnimalsFemaleMaleRatsRats, Inbred SHRRats, WistarAnti-inflammatoryBlood pressureCardiovascularHypertensionInflammationParaventricular nucleusRNA-SeqSex differencesTranscriptomics

Identifiers

PMID41723507
PMCPMC12964816

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.