Under moderate angiotensin II-induced hypertension, the 129S1/SvlmJ mouse strain developed severe target organ damage, including cognitive impairment and cardiac hypertrophy, unlike the C57BL/6J strain.
The 129S1/SvlmJ mouse strain is a more relevant translational model for severe hypertensive target organ damage than the commonly used C57BL/6J strain.
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.
Orieux et al. (Thu,) conducted a other in Hypertension. Angiotensin II vs. Saline infusion (0.9%) was evaluated on Target organ damage. Under moderate angiotensin II-induced hypertension, the 129S1/SvlmJ mouse strain developed severe target organ damage, including cognitive impairment and cardiac hypertrophy, unlike the C57BL/6J strain.