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Updated: Oct 5, 2026
Murine Myocardial Infarction Model using Permanent Ligation of Left Anterior Descending Coronary Artery
Published on: August 16, 2019
Possible roles of cardiac chymase after myocardial infarction in hamster hearts
Insights
Cardiac chymase activity significantly increases after myocardial infarction (MI) in hamsters. Angiotensin II receptor blockade improved survival and hemodynamics, suggesting chymase-derived Ang II contributes to post-MI pathology.
Area of Science:
- Cardiovascular Research
- Enzymology
- Pharmacology
Background:
- Myocardial infarction (MI) triggers complex cardiac remodeling processes.
- Cardiac chymase and angiotensin-converting enzyme (ACE) are implicated in cardiovascular disease.
- The specific role of cardiac chymase in post-MI pathophysiology remains to be fully elucidated.
Purpose of the Study:
- To evaluate the significance of cardiac chymase after myocardial infarction (MI) in a hamster model.
- To investigate the temporal changes in cardiac chymase and ACE activities post-MI.
- To assess the therapeutic effects of an angiotensin II receptor antagonist versus an ACE inhibitor on post-MI outcomes.
Main Methods:
- A hamster model of MI was established using left coronary artery ligation.
- Cardiac tissues were analyzed for chymase and ACE activities at various time points post-MI.
- Plasma renin activity and hemodynamic parameters were measured.
- Animals were treated with candesartan cilexetil (Ang II receptor antagonist) or lisinopril (ACE inhibitor) before and after MI.
Main Results:
- MI led to increased left ventricle weight and infarct size.
- Plasma renin activity increased early post-MI; cardiac ACE activity increased from day 3 to 28.
- Cardiac chymase activity and chymase-positive mast cells significantly increased from day 1 to 56 post-MI.
- Candesartan cilexetil reduced mortality and improved hemodynamics, while lisinopril did not show significant benefits.
Conclusions:
- Cardiac chymase activity is significantly upregulated following MI in hamsters.
- Chymase-derived angiotensin II may play a crucial role in the adverse pathophysiological changes after MI.
- Targeting the angiotensin II type 1 receptor with candesartan cilexetil offers therapeutic potential post-MI.
Abstract:
The significance of cardiac chymase after myocardial infarction (MI) was evaluated using a hamster model of MI. At 1, 3, 7, 14, 28 and 56 days after MI, tissues were removed for measurements of angiotensin-converting enzyme (ACE) and chymase activities. The mean infarct size 3 days after left coronary artery ligation was 47.3 +/- 5.9% of the left ventricle circumference. The ratio of left ventricle weight to body weight was significantly increased from 3 days after MI. The level of plasma renin activity in the MI hamsters was significantly increased at the early phase of MI (1-3 days), while no significant changes in plasma ACE activity were observed. The ACE activity in the infarcted left ventricle was significantly increased starting from 3 days after MI and this increase was sustained up to 28 days. The chymase activity in the infarcted left ventricle was significantly increased starting from 1 day after MI and this increase was sustained up to 56 days. The number of chymase-positive mast cells in the infarcted left ventricle was significantly higher than in the sham group 3 and 7 days after operation. Treatment with an angiotensin (Ang) II type 1 receptor antagonist (candesartan cilexetil, 10 mg/kg per day) starting 3 days before the induction of MI significantly reduced the mortality rate during 14 days of observation following MI, whereas treatment with an ACE inhibitor (lisinopril, 20 mg/kg per day) did not. A significant improvement in hemodynamics (maximal negative and positive rates of pressure development, left ventricular systolic pressure and end-diastolic pressure, mean arterial blood pressure) was observed by the treatment with candesartan cilexetil, but not with lisinopril, 3 and 14 days after MI. These results suggested that Ang II produced by chymase may participate in the pathophysiologic state after MI in hamsters.
