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 language | English (US) |
|---|---|
| Pages (from-to) | 131-139 |
| Number of pages | 9 |
| Journal | The EMBO journal |
| Volume | 22 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2 2003 |
Fingerprint
Keywords
- Aging
- Heart failure
- P53
- Telomerase
- Telomeres
ASJC Scopus subject areas
- Genetics
- Cell Biology
Cite this
Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation. / Leri, Annarosa; Franco, Sonia; Zacheo, Antonella; Barlucchi, Laura; Chimenti, Stefano; Limana, Federica; Nadal-Ginard, Bernardo; Kajstura, Jan; Anversa, Piero; Blasco, María A.
In: The EMBO journal, Vol. 22, No. 1, 02.01.2003, p. 131-139.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Ablation of telomerase and telomere loss leads to cardiac dilatation and heart failure associated with p53 upregulation
AU - Leri, Annarosa
AU - Franco, Sonia
AU - Zacheo, Antonella
AU - Barlucchi, Laura
AU - Chimenti, Stefano
AU - Limana, Federica
AU - Nadal-Ginard, Bernardo
AU - Kajstura, Jan
AU - Anversa, Piero
AU - Blasco, María A.
PY - 2003/1/2
Y1 - 2003/1/2
N2 - 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.
AB - 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.
KW - Aging
KW - Heart failure
KW - P53
KW - Telomerase
KW - Telomeres
UR - http://www.scopus.com/inward/record.url?scp=0037413726&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0037413726&partnerID=8YFLogxK
U2 - 10.1093/emboj/cdg013
DO - 10.1093/emboj/cdg013
M3 - Article
C2 - 12505991
AN - SCOPUS:0037413726
VL - 22
SP - 131
EP - 139
JO - EMBO Journal
JF - EMBO Journal
SN - 0261-4189
IS - 1
ER -