Abstract 16496: Circulating Systemic Factors From Young Mice Reverse Age-Related Cardiac Hypertrophy
Background. Although much progress has been made in the treatment of systolic heart failure, progress in diastolic heart failure has been decidedly more elusive. Here we tested the hypothesis that systemic circulating factors can reverse cardiac hypertrophy that can accompany aging, a process that may play a causative role in diastolic heart failure.
Methods. We used the parabiosis model, in which two mice are surgically joined such that they develop a shared blood circulation; in parabiosis, the mice continually exchange circulating cells and soluble factors at physiological levels through their common circulatory system. We generated heterochronic parabiotic pairs, in which young mice (2 months) were surgically joined to aged partners (23 months), and compared these to isochronic parabiotic pairs (young-young, or aged-aged), joined at identical ages, and to age- and sex-matched unpaired mice as controls. Blood pressures were recorded prior to study onset and periodically throughout the conjoined period. Mice were sacrificed after 4 weeks for analysis.
Results. We found no significant difference in LV cardiac myocyte cross-sectional area in young mice from any of the three different experimental conditions (186.7±4.9 µm2, n=4 in young controls, 243.1±12.1 µm2, n=12 in young isochronic, 232.2±16.4 µm2, n=6 in young heterochronic). Average cardiac myocyte size was significantly greater in the hearts of the old isochronic (357.8±25.8 µm2, n=12) and old non-parabiotic control hearts (348.3±12.6 µm2, n=4). However, aging hearts that were exposed for 4 wks to a young circulation (heterochronic-old group, n=6) showed a significant reduction of myocyte size when compared to the old isochronic (220.4±21.9 vs. 357.8±25.8 µm2, P<0.05). We did not detect a significant decrease in systemic blood pressure in aging mice exposed to a young circulation, suggesting that age-related hemodynamic factors cannot explain the reversal of cardiac aging.
Conclusions. Circulating systemic factors from young mice can reverse cardiac hypertrophy of aging mice. Because changes in blood pressure do not explain this reversal of age-related cardiac hypertrophy, these experiments suggest potential new avenues to treating diastolic heart failure.
- © 2011 by American Heart Association, Inc.