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Updated: Sep 28, 2026
Cardiac Pressure-Volume Loop Analysis Using Conductance Catheters in Mice
Published on: September 17, 2015
Time-dependent expression of chymase and angiotensin converting enzyme in the hamster heart under pressure overload
Peng Li1, Peng-Ming Chen, Shi-Wen Wang
1Cardiovascular Institute and Fu Wai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, PR China.
Insights
Cardiac hypertrophy involves dual angiotensin II pathways, chymase and ACE, activated by pressure overload. Increased enzyme activity, not just gene expression, drives Ang II production, contributing to heart enlargement.
Area of Science:
- Cardiovascular Biology
- Molecular Cardiology
- Renal Physiology
Background:
- Cardiac hypertrophy is a significant risk factor for heart failure.
- The renin-angiotensin system (RAS) plays a crucial role in cardiovascular regulation.
- Local cardiac RAS pathways are implicated in cardiac remodeling.
Purpose of the Study:
- To investigate the role of a dual angiotensin II-forming pathway involving chymase and angiotensin-converting enzyme (ACE) in cardiac hypertrophy.
- To determine the time-dependent changes in gene expression, enzyme activity, and Ang II levels in response to pressure overload.
Main Methods:
- Cardiac hypertrophy was induced in hamsters via abdominal aortic constriction.
- Time-course measurements of chymase and ACE gene expression, enzyme activities, and Ang II levels were performed.
- Cardiomyocyte diameter was assessed to confirm hypertrophy.
Main Results:
- Pressure overload led to significant increases in cardiomyocyte diameter, chymase and ACE gene expression, enzyme activities, and Ang II levels.
- Chymase and ACE activities increased disproportionately more than their mRNA levels.
- Chymase activity was higher than ACE activity during hypertrophy development.
- Chymase activation preceded mRNA increase and Ang II elevation in the early stage.
Conclusions:
- A dual pathway involving chymase and ACE contributes significantly to Ang II formation in pressure-overload-induced cardiac hypertrophy.
- Increased chymase and ACE enzyme activities, rather than solely gene expression, are key drivers of Ang II elevation.
- Chymase plays a critical early role, potentially activated by mechanical stress before transcriptional changes.
Abstract:
The role of a dual angiotensin (Ang) II-forming pathway from the local renin angiotensin system (RAS) of the cardiac tissue was determined in a hamster model of cardiac hypertrophy. Time-dependent expressions of chymase and angiotensin converting enzyme (ACE) genes and their enzymes activities, and Ang II levels were measured in the hamster heart at 3 days, and at 4 and 8 weeks after pressure overload. Cardiac hypertrophy was induced by an operation to constrict the abdominal aorta. Compared to the sham-operated group, the cardiomyocyte diameters of hamster hearts at 3 days after overload underwent no obvious changes, while those at 4 and 8 weeks after overload increased markedly (p<0.01), and both transcriptional expressions of chymase and ACE genes gradually increased in the hamster hearts at 3 days, and at 4 and 8 weeks after overload, but the transcriptional expressions of angiotensin II type 1 receptor (AT1R) gene gradually decreased. Chymase and ACE activities (U/mg) (0.441+/-0.040 vs. 0.175+/-0.014, 0.446+/-0.036 vs. 0.160+/-0.016 and 0.522+/-0.014 vs. 0.148+/-0.038) (p<0.01) and (0.142+/-0.023 vs. 0.056+/-0.038, 0.317+/-0.017 vs. 0.079+/-0.016 and 0.466+/-0.010 vs. 0.098+/-0.003) (p<0.01), respectively and Ang II levels (pg/g) (98.7+/-4.5 vs. 71.2+/-4.9, 134.4+/-7.8 vs. 71.9+/-12.8 and 151.6+/-10.1 vs. 80.7+/-3.0) gradually increased in the hamster hearts, vs. sham treatment, respectively, at 3 days, and at 4 and 8 weeks after overload. However, the increases in chymase and ACE activities were much higher than those in their respective mRNA levels, and the levels of chymase activities were also higher than those of ACE activities during the development of cardiac hypertrophy. The results suggested that the increase in Ang II levels via the dual pathway of Ang II formation by chymase and ACE plays an important role in the cardiac hypertrophy of hamsters caused by the overloaded state. Importantly, in the non-hypertrophied hamster heart in the early stage after overload (at 3 days), chymase could be activated by mechanical stress in advance of an increase in its mRNA, and the Ang II level increased significantly.
