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The angiotensin II type 2 receptor and improved adjacent region function post-MI
Christina M Bove1, Wesley D Gilson, Christopher D Scott
1Department of Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Summary
Overexpression of the Angiotensin II type 2 receptor (AT2-R) in mice hearts improves regional heart muscle function in areas adjacent to infarction. This AT2-R cardiac overexpression preserves overall left ventricular function after myocardial infarction.
Area of Science:
- Cardiovascular Research
- Molecular Cardiology
- Regenerative Medicine
Background:
- Myocardial infarction (MI) triggers adverse cardiac remodeling, impairing left ventricular (LV) function.
- Angiotensin II type 2 receptor (AT2-R) overexpression has shown potential in preserving cardiac structure and function post-MI.
- Regional functional deficits after MI are critical determinants of global LV performance.
Purpose of the Study:
- To investigate if cardiac AT2-R overexpression improves regional myocardial function post-MI using cardiac magnetic resonance (CMR) tagging.
- To determine if regional functional improvements in AT2-R overexpressing mice explain preserved global LV function.
- To localize functional changes within infarcted, adjacent, and remote myocardial regions.
Main Methods:
- Utilized transgenic (TG) mice overexpressing AT2-R and wild-type (WT) littermates.
- Induced myocardial infarction (MI) via LAD occlusion and reperfusion.
- Assessed LV size, global function, and infarct size using cine and contrast-enhanced CMR.
- Employed CMR tagging to quantify regional myocardial strain (%CS) in infarcted, adjacent, and remote zones.
- Performed postmortem histological analysis of interstitial collagen and myocyte size.
Main Results:
- TG mice maintained higher LV ejection fraction and lower end-systolic volume compared to WT mice, both at baseline and post-MI.
- While differences in %CS were transient in infarcted and remote zones, TG mice showed significantly higher %CS in adjacent regions by day 7 post-MI, persisting to day 28.
- No significant differences in regional interstitial collagen or myocyte cross-sectional area were observed between groups at day 28.
- CMR tagging successfully identified regional functional improvements in the adjacent myocardium of TG mice.
Conclusions:
- Cardiac AT2-R overexpression enhances contractile function in the non-infarcted myocardium adjacent to the infarct zone post-MI.
- These regional functional improvements contribute to the preservation of global LV function observed in AT2-R overexpressing mice.
- CMR tagging is a valuable tool for detecting regional myocardial functional changes after MI in preclinical models.