Telomerase expression and activity are coupled with myocyte proliferation and preservation of telomeric length in the failing heart

Annarosa Leri, Laura Barlucchi, Federica Limana, Andrzej Deptala, Zbigniew Darzynkiewicz, Thomas H. Hintze, Jan Kajstura, Bernardo Nadal-Ginard, Piero Anversa

Research output: Contribution to journalArticlepeer-review

Abstract

The role and even the existence of myocyte proliferation in the adult heart remain controversial. Documentation of cell cycle regulators, DNA synthesis, and mitotic images has not modified the view that myocordial growth can only occur from hypertrophy of an irreplaceable population of differentiated myocytes. To improve understanding the biology of the heart and obtain supportive evidence of myocyte replication, three indices of cell proliferation were analyzed in dogs affected by a progressive deterioration of cardiac performance and dilated cardiomyopathy. The magnitude of cycling myocytes was evaluated by the expression of Ki67 in nuclei. Ki67 labeling of left ventricular myocytes increased 5-fold, 12-fold and 17-fold with the onset of moderate and severe ventricular dysfunction and overt failure, respectively. telomerase activity in vivo is present only in multiplying cells; this enzyme increased 2.4-fold and 3.1-fold in the decompensated heart, preserving telomeric length in myocytes. The contribution of cycling myocytes to telomerase activity was determined by the colocalization of Ki67 and telomerase in myocyte nuclei. More than 50% of Ki67-positive cells expressed telomerase in the overloaded myocardium, suggesting that these myocytes were the morphological counterpart of the biochemical assay of enzyme activity. Moreover, we report that 20-30% of canine myocytes were telomerase competent, and this value was not changed by cardiac failure. In conclusion, the enhanced expression of Ki67 and telomerase activity, in combination with Ki67-telomerase labeling of myocyte nuclei, support the notion that myocyte proliferation contributes to cardiac hypertrophy of the diseased heart.

Original languageEnglish
Pages (from-to)8626-8631
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number15
DOIs
Publication statusPublished - Jul 17 2001

ASJC Scopus subject areas

  • Genetics
  • General

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