Key result
Mice expressing a gain-of-function mutant of the angiotensin II type 1A receptor developed a moderate, stable increase in systolic blood pressure along with early and progressive cardiac and renal fibrosis.
Why the study?
Does constitutive activation of the AT1A receptor cause hypertension and cardiovascular fibrosis in mice?
Population
Homozygous knockin mouse model expressing a gain-of-function mutant of the Ang II receptor, type 1A and…
Comparison
Constitutive activation of the AT1A receptor via… vs Wild-type (WT) littermates.
Design
Preclinical
Follow-up
Up to 12-15 months of age
Authors
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This AT1A gain-of-function mouse model remains preliminary; leaves open translation to human low-renin hypertension and fibrosis.
Does constitutive activation of the AT1A receptor cause hypertension and cardiovascular fibrosis in mice?
Mean Difference: 27
Absolute Event Rate: 122% vs 95%
p-value: p=<0.01
A novel mouse model with constitutively active AT1A receptors demonstrates that AT1A activation leads to cardiac and renal fibrosis and diastolic dysfunction despite only modest blood pressure elevation, mimicking low-renin human hypertension.
Billet et al. (2007) studied Hypertension and cardiovascular fibrosis. AT1A N111S/Δ329 mutation vs. Wild-type (AT1AWT) littermates was evaluated on Systolic blood pressure (mmHg) (MD 27 mmHg, p=<0.01). Mice expressing a gain-of-function mutant of the angiotensin II type 1A receptor developed a moderate, stable increase in systolic blood pressure along with early and progressive cardiac and renal fibrosis.
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