Abstract
Hypertension remains the leading cause of cerebral, cardiac, renal, and retinal vascular damage. However, genetic determinants underlying organ-specific vulnerability are poorly understood, and commonly used mouse models, notably C57BL/6J, often fail to recapitulate severe hypertensive complications seen in humans. This study compares the widely used C57BL/6J mouse strain with the genetically distinct 129S1/SvlmJ strain under hypertensive stress, aiming to identify a model that better reproduces hypertensive target organ damage. Moderate hypertension was induced in 129S1/SvlmJ and C57BL/6J mice using chronic infusion of angiotensin II (600 ng/kg/min). Despite comparable blood pressure elevations, only 129S1/SvlmJ mice developed severe organ damage, including cognitive impairment, pronounced blood-brain barrier disruption, retinal vasculopathy, cardiac hypertrophy, and podocyte lesions with albuminuria. In contrast, C57BL/6J mice exhibited markedly less organ injury under the experimental conditions tested. Transcriptomic analysis of cerebral microvessels identified distinct inflammatory and immune-related signatures between strains, paralleling their vascular phenotypes. These immune profiles appear as hallmarks of strain-specific susceptibility rather than as direct protective or deleterious mechanisms. This study demonstrates that genetic background critically shapes hypertensive complications, identifying the 129S1/SvlmJ strain as a relevant and translational model of hypertensive target organ damage. Beyond reproducing key features of severe hypertension, this model provides a framework to investigate the pathways linking genetic susceptibility, vascular injury, and end-organ damage.
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Data availability
The datasets generated and/or analysed during the current study are available in the ArrayExpress repository number E-MTAB-15937 : https://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-15937.
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Acknowledgements
We sincerely thank Béatrice JASPARD-VINASSA and Muriel BUSSON for scientific advice, Philippe ALZIEU, Sylvain GROLLEAU, Maxime DAVID for their technical assistance and animal care; Christelle BOULLE and Hélène AOUIZERATE for administrative assistance. We thank Prof. Céline GUILBEAU-FRUGIER (UMR 1297, Toulouse, France) for Electron Microscopy images. This work benefited from equipment and services from the PCRq’UB platform (Bordeaux University). We thank Fondation pour la Recherche Médicale (FRM) for it support)
Funding
Arthur ORIEUX (salary grant) : MD-PhD student grant – CHU de Bordeaux et Université de Bordeaux. Bourse Société Francophone de Néphrologie Dialyse et Transplantation (SFNDT) 2023. This project is supported by a grant overseen by the French National Research Agency (ANR) as part of the Investment for the Future Programme ANR-18-RHUS-0002 (SHIVA Project) and by the Precision and Global Vascular Brain Health Institute (VBHI) funded by the France 2030 IHU3 initiative.
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Data acquisition : Maxime Michot, Juliette Vaurs, Marie-Lise Bats, Virginie Dinet, Romain BoulestreauData acquisition, analysis and interpretation of data : Arthur Orieux Marie-Lise Bats and Sébastien RubinConception or design of the work : Sébastien Rubin, Cécile Duplaa, Thierry CouffinhalDrafting the work : Arthur Orieux and Sébastien RubinReviewing the manuscript Sébastien Rubin, Cécile Duplaa, Thierry Couffinhal, Alexandre Boyer, Claire Peghaire and Pascale DufourcqImportant intellectual content : Sébastien Rubin, Cécile Duplaa, Thierry Couffinhal, Claire Peghaire.
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Orieux, A., Boulestreau, R., Bats, ML. et al. The 129S1/SvlmJ mouse strain recapitulates severe hypertensive target organ damage under moderate angiotensin II–induced hypertension. Sci Rep (2026). https://doi.org/10.1038/s41598-026-41288-7
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DOI: https://doi.org/10.1038/s41598-026-41288-7
