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Interaction between AT1 and AT2 receptors during postinfarction left ventricular remodeling
Szilard Voros1, Zequan Yang, Christina M Bove
1Department of Medicine, University of Virginia Health System, Lee St., Box 800170, Charlottesville, Virginia 22908, USA.
American Journal of Physiology. Heart and Circulatory Physiology
|October 11, 2005
Summary
The angiotensin II type 2 receptor (AT2-R) and type 1 receptor (AT1-R) play key roles in heart remodeling after myocardial infarction (MI). Blocking AT1-R or overexpressing AT2-R improves cardiac function and reduces adverse remodeling post-MI.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Medical Research
Background:
- The roles of angiotensin II receptors (AT1-R and AT2-R) in post-myocardial infarction (MI) cardiac remodeling are not fully understood.
- Understanding these roles is crucial for developing targeted therapies to improve heart function after MI.
Purpose of the Study:
- To investigate the distinct and combined contributions of AT1-R and AT2-R in cardiac remodeling following MI.
- To compare the effects of AT1-R blockade and AT2-R overexpression on post-MI cardiac remodeling.
Main Methods:
- Five groups of C57Bl/6 mice were studied after induced MI: wild type (untreated and losartan-treated), AT2-receptor transgenic (AT2-TG), AT2-TG with losartan, and AT2-TG/AT1a-receptor knockout (KO).
- Cardiac magnetic resonance imaging (CMR) assessed cardiac function and structure.
- Infarct size, myocyte hypertrophy, and collagen content were analyzed post-MI.
Main Results:
- Infarct size was similar across all groups.
- Wild-type mice showed significantly worse cardiac remodeling (higher volumes, lower ejection fraction) compared to other groups by day 28 post-MI.
- The AT2-TG/AT1a-KO group exhibited the best outcomes, with the highest ejection fraction and lowest cardiac volumes and mass, along with reduced fibrosis.
- Pharmacological AT1-R blockade was comparable to AT2-R overexpression in attenuating remodeling, while genetic AT1a-R knockout added to AT2-R overexpression benefits, partly via blood pressure reduction.
Conclusions:
- AT1-R and AT2-R are intricately involved in post-MI cardiac remodeling.
- Blocking AT1-R is as effective as AT2-R overexpression in mitigating adverse remodeling.
- Genetic deletion of AT1a-R enhances the benefits of AT2-R overexpression, suggesting a synergistic effect partly mediated by blood pressure modulation.