Abstract 19706: Cardiomyocyte-Specific Telomere Shortening is a Distinct Signature of Heart Failure in Human
Background: Hypertrophic cardiomyopathy (HCM) is a clinically heterogeneous disorder with serious adverse outcomes. Despite efforts, current treatments entail only supportive strategies as detailed mechanisms behind HCM etiology are not fully uncovered. Extensive studies are carried out to link phenotype with genotype in patients. Our team recently recognized the role of distal ends of chromosomes, called telomeres, in unveiling cardiac disease phenotype. In proliferative cells, telomere shortening occurs with each cell division. Importantly, however, the role of telomere attrition in the setting of heart failure and specifically in human adult cardiomyocytes, as post-mitotic cells, is equivocal.
Methods: We prospectively studied cardiac tissues from healthy individuals (n=27) and HCM patients (n=37) by optimizing telomere quantitative fluorescence in situ hybridization (Q-FISH), a highly sensitive method with single-cell resolution.
Results: Our results demonstrate that patients with HCM have shorter telomeres compared with healthy individuals. In fact, the observed telomere shortening is specific to cardiomyocytes and not to other cell types within the same cardiac tissues, arguing against universal telomere shortening. Interestingly, longest cardiomyocyte telomere lengths were observed in patients with preserved ejection fraction and sustained hypertrophy, illustrating a strong correlation between telomere length and cardiac function. We further found that, in contrast to other reported cell types, no telomere shortening was evident with age in cardiomyocytes of healthy hearts. However, under disease condition, telomere attrition occurred regardless of age suggesting that the cardiac telomere defect is not age-dependent and it solely occurs under the disease state. We further demonstrate that females have longer telomeres regardless of the presence or absence of disease, which may contribute to the well-known lower prevalence of females with HCM.
Conclusion: Our data provide the first clear evidence that cardiomyocyte-specific telomere shortening is a hallmark of human heart failure and highlights its significance in aging and gender and suggest possible new therapeutic avenues important in cardiomyocyte function.
Author Disclosures: M. Sharifi-Sanjani: None. N. Oyster: None. K. Bedi: None. K. Margulies: None. F. Mourkioti: None.
- © 2016 by American Heart Association, Inc.