Related Experiment Video
Updated: Mar 9, 2026
Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
Published on: June 29, 2014
Ascending Aortic Constriction Promotes Cardiomyocyte Proliferation in Neonatal Rats
Zhenhua Wang1, Sebastian Schmull, Hui Zheng
1Department of Cardiovascular Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University.
Insights
Neonatal hearts can regenerate after injury. Ascending aortic constriction in newborn rats stimulated cardiomyocyte proliferation, increasing cell numbers and improving heart function within the first week of life.
Area of Science:
- Cardiovascular Biology
- Neonatal Physiology
- Cardiac Regeneration
Background:
- Adult hearts undergo hypertrophy and failure under increased workload.
- The response of neonatal hearts to increased afterload is not well understood.
Purpose of the Study:
- To investigate the effect of increased afterload on neonatal rat heart function and cardiomyocyte proliferation.
- To determine if neonatal cardiomyocytes can re-enter the cell cycle and proliferate in response to mechanical stress.
Main Methods:
- Ascending aortic constriction (AAC) was performed on neonatal rats (P0).
- Cardiac function was assessed using echocardiography.
- Histological analysis (H&E, Masson) evaluated cardiomyocyte diameter and collagen deposition.
- Cell proliferation markers (EdU, Ki67) and mitosis markers (pH3, aurora B) were quantified.
- Cardiomyocyte counts were determined via cell isolation and perfusion.
Main Results:
- AAC significantly increased cardiomyocyte cell cycle activation and proliferation.
- Constricted hearts showed increased wall thickness and improved ejection fraction by P7.
- The total number of cardiomyocytes increased by 16.7% in the constriction group compared to controls.
- Neonatal cardiomyocytes demonstrated the capacity to re-enter the cell cycle within the first postnatal week.
Conclusions:
- Neonatal rat cardiomyocytes can proliferate in response to increased afterload.
- Ascending aortic constriction promotes cardiomyocyte proliferation and enhances cardiac function in the early postnatal period.
- This study highlights the potential for cardiac regeneration in the neonatal heart.
Abstract:
Adult heart suffering from increased workload will undergo myocardial hypertrophy, subsequent cardiomyocyte (CM) death, and eventually heart failure. However, the effect of increasing afterload on the neonatal heart remains unknown. We performed ascending aortic constriction (AAC) in neonatal rats 8-12 hours after birth (P0, P indicates postpartum). Seven days after surgery, in vivo heart function was evaluated using cardiac ultrasonography. Haematoxylineosin and Masson staining were used to assess CM diameter and collagen deposition. Moreover, expression of both EdU and Ki67 were evaluated to determine DNA synthesis levels, and pH3 and aurora B as markers for mitosis in CMs. CM isolation was performed by heart perfusion at P0, P3, P5, and P7, respectively. CM number on P0 was 1.01 ± 0.29 × 106. We found that CM cell cycle activation was significantly increased among constricted hearts, as demonstrated by increased Ki67, EdU, pH3, and aurora B positive cells/1000 CMs. At day 7 (P7), constriction group hearts manifested increased wall thickness (0.55 ± 0.05 mm versus 0.85 ± 0.10 mm, P < 0.01, n = 6), and improved hemodynamics as well as left ventricular ejection fraction (65.5 ± 3.7% versus 77.7 ± 4.8%, P < 0.01, n = 6). Of note, the population of CMs was also markedly increased in the constriction group (2.92 ± 0.27 × 106 versus 3.41 ± 0.40 × 106, P < 0.05, n = 6). In summary, we found that during the first week after birth significant numbers of neonatal CMs can reenter the cell cycle. Ascending aortic constriction promotes neonatal rat CM proliferation resulting in 16.7% more CMs in the heart.
