Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation

Annarosa Leri, Sonia Franco, Antonella Zacheo, Laura Barlucchi, Stefano Chimenti, Federica Limana, Bernardo Nadal-Ginard, Jan Kajstura, Piero Anversa, María A. Blasco

Research output: Contribution to journalArticle

Abstract

Cardiac failure is a frequent cause of death in the aging human population. Telomere attrition occurs with age, and is proposed to be causal for the aging process. To determine whether telomere shortening leads to a cardiac phenotype, we studied heart function in the telomerase knockout mouse, Terc-/-. We studied Terc-/-mice at the second, G2, and fifth, G5, generation. Telomere shortening in G2 and G5 Terc-/- mice was coupled with attenuation in cardiac myocyte proliferation, increased apoptosis and cardiac myocyte hypertrophy. On a single-cell basis, telomere shortening was coincidental with increased expression of p53, indicating the presence of dysfunctional telomeres in cardiac myocytes from G5 Terc-/-mice. The impairment in cell division, the enhanced cardiac myocyte death and cellular hypertrophy, are concomitant with ventricular dilation, thinning of the wall and cardiac dysfunction. Thus, inhibition of cardiac myocyte replication provoked by telomere shortening, results in de-compensated eccentric hypertrophy and heart failure in mice. Telomere shortening with age could also contribute to cardiac failure in humans, opening the possibility for new therapies.

Original languageEnglish (US)
Pages (from-to)131-139
Number of pages9
JournalThe EMBO journal
Volume22
Issue number1
DOIs
StatePublished - Jan 2 2003

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Keywords

  • Aging
  • Heart failure
  • P53
  • Telomerase
  • Telomeres

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Leri, A., Franco, S., Zacheo, A., Barlucchi, L., Chimenti, S., Limana, F., Nadal-Ginard, B., Kajstura, J., Anversa, P., & Blasco, M. A. (2003). Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. The EMBO journal, 22(1), 131-139. https://doi.org/10.1093/emboj/cdg013