Abstract 15929: Cardiosphere-derived Cells From Young Rats Improve Diastolic Function, Exercise Capacity and Age-associated Biomarkers in Senescent Rats
Introduction: Aging is associated with diastolic dysfunction and global functional impairment. Despite its increasing prevalence, age-related diastolic heart failure is refractory to conventional treatment approaches. Cardiosphere-derived cell (CDC) therapy attenuates diastolic dysfunction in young hypertensive rats; however, the effects of CDCs on age-related heart dysfunction have not been studied.
Objectives: 1) To evaluate the effects of young CDCs on heart structure and function in aged rats. 2) To test young CDCs’ capacity to improve global function and serum biomarkers in aged rats.
Methods: Neonatal rat CDCs (n=11) or phosphate-buffered saline (PBS, n=11) were injected into hearts of 21-25 month-old rats. Two and 7-month-old rats served as comparators (n=10). Serum biomarkers, echos, invasive hemodynamics and treadmill exercise tests were evaluated at baseline and 1-month after treatment in old animals, and at baseline in young animals.
Results: Old animals exhibit diastolic dysfunction with increased ventricular stiffness [higher mitral E/A (p<0.01) and E/E’ (p<0.01) with impaired relaxation [higher Tau (p<0.01) and lower min Dp/Dt (p<0.001)] compared with younger controls. Exercise capacity was dramatically reduced in aged rats (r=0.76, p<0.001). CDC treatment decreased stiffness [decrease of E/A (p<0.01), E/E’ (p=0.05), and downward displacement of the end-diastolic pressure-volume relationship (p<0.05) compared with baseline] and accelerated relaxation [Tau (p<0.05) vs. PBS-treated animals]. Exercise capacity increased ~20% in CDC-treated old rats (p<0.05 compared with baseline), but not in controls. They also lost 30% less body weight (p=0.05 vs. PBS group), had lower serum brain natriuretic peptide (p<0.05 vs. PBS group) and creatinine levels (p=0.05 compared to baseline). Hair regrowth was also more robust in CDC-treated old rats.
Conclusion: Young CDCs induce rejuvenation in old animals: they improve heart function and global exercise capacity while exhibiting various other positive systemic effects. Given the paucity of viable approaches to combat aging, CDC transplantation may merit further testing as a therapeutic strategy against age-related cardiovascular diseases and global functional decline.
Author Disclosures: L. Grigorian: None. S. Fereydooni: None. W. Liu: None. R. Middleton: None. J. Cho: None. J. Valle: None. A. Echavez: None. E. Marbán: Ownership Interest; Modest; Capricor. Consultant/Advisory Board; Modest; Capricor.
- © 2016 by American Heart Association, Inc.