Related Experiment Video
Updated: Feb 17, 2026
Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
Published on: June 29, 2014
Accelerated decline in cardiac stem cell efficiency in Spontaneously hypertensive rat compared to normotensive Wistar
Sherin Saheera1, Renuka R Nair1
1Division of Cellular and Molecular Cardiology, Sree Chitra Tirunal Institute for Medical Sciences and Technology, Trivandrum, Thiruvananthapuram, Kerala, India.
Insights
Cardiac stem cell (CSC) efficiency declines with age, a process accelerated in Spontaneously Hypertensive Rats (SHR). This age-associated decline in healthy CSCs, exacerbated by oxidative stress in SHR, may precipitate cardiac decompensation in hypertensive heart disease.
Area of Science:
- Cardiovascular Biology
- Stem Cell Research
- Aging and Disease
Background:
- Cardiac hypertrophy is a key risk factor for heart failure, necessitating understanding of transition mechanisms.
- Resident cardiac stem cells (CSCs) are crucial for cardiac tissue homeostasis and regeneration.
- Pathological conditions and aging can impair CSC function, but systematic analysis is lacking.
Purpose of the Study:
- To investigate age-associated variations in cardiac stem cell attributes in Spontaneously Hypertensive Rats (SHR) versus normotensive Wistar rats.
- To identify factors contributing to the decline of CSC efficiency in the context of hypertensive heart disease.
Main Methods:
- Isolation of CSCs from atrial explants of male SHR and Wistar rats at 1 week, 6, 12, and 18 months of age.
- Assessment of stem cell attributes including migration, proliferation, TERT expression, telomerase activity, c-kit+ cell proportion, DNA damage, senescence, and oxidative stress.
- Comparative analysis of CSC characteristics between SHR and Wistar rats across different age groups.
Main Results:
- CSCs from both SHR and Wistar rats showed age-related decreases in migration, proliferation, TERT expression, telomerase activity, and c-kit+ cells.
- DNA damage and senescence increased with age in both rat groups, alongside heightened oxidative stress.
- These age-associated declines were significantly more pronounced and occurred earlier in SHR, with reduced CSC efficiency noted as early as six months.
Conclusions:
- Age-associated decline in functionally efficient CSCs is accelerated in SHR, potentially contributing to pathological cardiac remodeling.
- Elevated oxidative stress in SHR CSCs suggests a mechanism for impaired stem cell function.
- Therapeutic modulation of the microenvironment may restore CSC function, aiding cardiac homeostasis and preventing decompensation.
Abstract:
Cardiac hypertrophy is recognized as an independent risk factor for cardiac failure. Efficient management of hypertensive heart disease requires identification of factors that can possibly mediate the transition from hypertrophy to failure. Resident cardiac stem cells have a prominent role in the maintenance of cardiac tissue homeostasis. Decline in the proportion of healthy cardiac stem cells (CSCs) can affect tissue regeneration. In pathological conditions, apart from natural aging, an adverse microenvironment can lead to decrease in efficiency of CSCs. A systematic analysis of cardiac stem cell characteristics in pathological conditions has not been reported so far. Therefore, this study was designed with the objective of examining the age associated variation in stem cell attributes of Spontaneously hypertensive rat (SHR) in comparison with normotensive Wistar rat. Spontaneously hypertensive rat was used as the experimental model since the cardiac remodeling resembles the clinical course of hypertensive heart disease. CSCs were isolated from atrial explants. Stem cell attributes were assessed in 1-week, 6, 12 and 18-month-old male SHR, in comparison with age matched Wistar rats. In 1-week-old pups, stem cell attributes of SHR and Wistar were comparable. Migration potential, proliferative capacity, TERT expression, telomerase activity and the proportion of c-kit+ cells decreased with age, both in SHR and Wistar. DNA damage and the proportion of senescent CSCs increased with age both in SHR and Wistar rats. Age associated increase was observed in the oxidative stress of stem cells, possibly mediated by the enhanced oxidative stress in the microenvironment. The changes were more pronounced in SHR, and as early as six months of age, there was significant decrease in efficiency of CSCs of SHR compared to Wistar. The density of healthy CSCs determined as a fraction of the differentiated cells was remarkably low in 18-month-old SHR. Age associated decrease in functionally efficient CSCs was therefore accelerated in SHR. Considering the vital role of CSCs in the maintenance of a healthy myocardium, decrease in functionally efficient CSCs can be a precipitating factor in pathological cardiac remodeling. Elevated ROS levels in CSCs of SHR lends scope for speculation that decrease in efficiency of CSCs is mediated by oxidative stress; and that modulation of the microenvironment by therapeutic interventions can restore a healthy stem cell population and facilitate maintenance of cardiac homeostasis and prevent cardiac decompensation.
