Direct Renin Inhibitor Attenuates Left Ventricular Remodeling in Post-Myocardial Infarction Heart Failure Mice
Ning-I Yang1, Chia-Chi Liao1, Ming-Jui Hung1
1Division of Cardiology, Chang Gung University College of Medicine, Chang Gung Memorial Hospital, Keelung, Taiwan.
Background:
The role of direct renin inhibitors in myocardial ischemia-induced heart failure is controversial. We hypothesized that direct renin inhibitors play a positive role, affecting in vivo myocardial function as well as in vitro extracellular matrix change.
Methods:
Ten-week-old C57BL/6J male mice with 2-kidney 1-clip (2K1C) model were enrolled in this study. The mice were divided into 3 groups each with 18 mice; group 1 sham-operated, group 2 coronary artery ligation- induced heart failure, and group 3 coronary artery ligation-induced heart failure receiving aliskiren minipump infusion. These mice were assessed for systemic hemodynamics and left ventricular function by 2-dimensional echocardiography (iE33, Philips). Myocardial tissue was stained and crude protein was isolated from the non- ischemic viable left ventricle. Myocardial tissue contents of anti-angiotensin II type 1 (AT1) receptor, matrix metalloproteinase (MMP)-2 and MMP-9 were examined.
Results:
There were 54 mice that received 2K1C and were followed up for three weeks. Baseline characteristics showed no difference. At follow-up, the heart failure-only group had greater left ventricular mass and worse systolic function as compared to the sham group. Whereas the heart failure-aliskiren group had lower left ventricle mass and better systolic function as compared to the heart failure-only group. AT1 receptor, MMP-2 and MMP-9 levels were increased in the heart failure-only model while direct renin inhibitor attenuated this significantly.
Conclusions:
Direct renin inhibitors improved myocardial function in a myocardial ischemia-induced heart failure mouse model. The improvement seen is present in myocardial mass, left ventricular systolic function and also in myocardial interstitial tissue.
Key Words:
Direct renin inhibitor; Echocardiography; Heart failure.
Insights
Direct renin inhibitors improved heart function and reduced adverse cardiac remodeling in a mouse model of heart failure. This study suggests a beneficial role for direct renin inhibitors in managing myocardial ischemia-induced heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Physiology
Background:
- The efficacy of direct renin inhibitors in myocardial ischemia-induced heart failure remains debated.
- This study investigates the impact of direct renin inhibitors on myocardial function and extracellular matrix changes.
Purpose of the Study:
- To evaluate the role of direct renin inhibitors in a mouse model of myocardial ischemia-induced heart failure.
- To assess the effects of direct renin inhibitors on in vivo myocardial function and in vitro extracellular matrix remodeling.
Main Methods:
- A 2-kidney 1-clip (2K1C) mouse model with coronary artery ligation was used.
- Mice were divided into sham-operated, heart failure, and heart failure with aliskiren treatment groups.
- Echocardiography assessed cardiac function, and myocardial tissue analysis examined AT1 receptor, MMP-2, and MMP-9 levels.
Main Results:
- Aliskiren treatment significantly reduced left ventricular mass and improved systolic function compared to the heart failure-only group.
- Direct renin inhibitor administration attenuated the increase in AT1 receptor, MMP-2, and MMP-9 levels observed in the heart failure model.
Conclusions:
- Direct renin inhibitors demonstrated a positive effect on myocardial function in ischemia-induced heart failure.
- Improvements were observed in myocardial mass, left ventricular systolic function, and myocardial interstitial tissue.
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