Abstract 569: Both Young and Old ACE2-transgenic Mice are More Resistant to Cardiac Dysfunction Induced by Myocardial Infarction
Background: Increased activity of the classic renin-angiotensin system (RAS) is associated with cardiovascular diseases (CVD) such as heart failure and hypertension. Angiotensin-converting enzyme 2 (ACE2) is reported to provide a protective role in CVD. In addition, there is a shift in the balance of the ACE2/Angiotensin-(1-7) axis towards the ACE/Angiotensin II axis during aging, making the cardiovascular system more vulnerable to damages. We hypothesized that global ACE2-overexpression could correct the imbalance between the two axes by providing a cardiovascular protective role against heart failure both in young and aged mice.
Methods: Both young (10 weeks old) and old (12 months old) ACE2-transgenic and wild type (WT) mice underwent myocardial infarction surgery. Cardiac function was measured using echocardiography four weeks after MI. The number of circulating inflammatory cells (CD11b) in the blood for these animals was also measured using flow cytometry.
Results: In the MI animals, the WT-old mice had a significant reduction in ejection fraction (47.67±4.23%: from 72.63±8.52% to 24.96±4.29%). However, the reduction in EF for ACE2-old mice was 37% lower (26.26±1.90%: from 60.06±7.56% to 29.18±5.66%) than that of WT-old mice. Meanwhile, the MI-induced decrease in EF of 14.60±1.56% for ACE2-young mice (from 59.09±8.38% to 44.49±6.82%) also was significantly less than the 26.97±1.21% reduction observed in WT-young mice (from 53.23±7.67% to 26.26±6.46%). Thus, ACE2 overexpression provides some protection of cardiac function from ischemia-induced injury in both young and old animals. Moreover, the circulating monocytes and macrophages in the blood of ACE2-young MI mice (22.65±6.86%) was also less than which observed in the WT control (31.37±4.90%), suggesting that there is less cardiac damage in these animals.
Conclusions: Collectively, our observation suggests that global ACE2 overexpression has a consistent cardiac protection both in the young and old and as a result, the heart may be more resistant to heart failure damage during aging. This protective effect may be partly due to its systematic anti-inflammatory effect.
- © 2013 by American Heart Association, Inc.