Protective effect of antioxidant Tempol on cardiac stem cells in chronic pressure overload hypertrophy

Cardiac hypertrophy, an independent risk factor for cardiac failure; is associated with oxidative stress. Decline in the proportion of healthy cardiac stem cells (CSCs), possibly mediated by oxidative stress can lead to cardiac failure. The present study was carried out to examine the hypothesis that reduction of oxidative stress restores CSC efficiency and prevents progressive cardiac remodelling.

Six-month old Spontaneously hypertensive rats (SHR) were supplemented with the antioxidant Tempol (20 mg/kg/day) for 14 days. The effect of Tempol on blood pressure and heart were assessed in SHR. Cardiac stem cells were isolated from atrial explants and expanded in culture for assessment of stem cell characteristics. Intracellular reactive oxygen species (ROS), proliferation, migration and senescence were evaluated in cultured atrial CSCs.

Tempol treatment reduced blood pressure, regressed cardiac hypertrophy and reduced oxidative stress in SHR. Compared to Wistar rat, the efficiency of CSCs was significantly compromised in SHR. Tempol reduced intracellular ROS and restored migration potential and proliferative capacity along with reduction of senescent CSCs and expression of senescence proteins p16^ink4a and p21.

Restoration of functional efficiency of CSCs by antioxidants signifies the role of oxidative stress in deterioration of stem cell attributes in the hypertrophic heart. The observations envisage the use of antioxidants as adjuvant medication for maintaining a healthy stem cell population, which can in-turn prevent progressive cardiac remodelling, a major determinant of cardiac failure.