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<p>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.</p>

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The 129S1/SvlmJ mouse strain recapitulates severe hypertensive target organ damage under moderate angiotensin II–induced hypertension

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年3月5日

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  • Arthur Orieux,
  • Romain Boulestreau,
  • Marie-Lise Bats,
  • Maxime Michot,
  • Alexandre Boyer,
  • Virginie Dinet,
  • Juliette Vaurs,
  • Pascale Dufourcq,
  • Claire Peghaire,
  • Cécile Duplaa,
  • Thierry Couffinhal,
  • Sébastien Rubin

摘要

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.