TY - JOUR
T1 - Effects of age and heart failure on human cardiac stem cell function
AU - Cesselli, Daniela
AU - Beltrami, Antonio P.
AU - D'Aurizio, Federica
AU - Marcon, Patrizia
AU - Bergamin, Natascha
AU - Toffoletto, Barbara
AU - Pandolfi, Maura
AU - Puppato, Elisa
AU - Marino, Laura
AU - Signore, Sergio
AU - Livi, Ugolino
AU - Verardo, Roberto
AU - Piazza, Silvano
AU - Marchionni, Luigi
AU - Fiorini, Claudia
AU - Schneider, Claudio
AU - Hosoda, Toru
AU - Rota, Marcello
AU - Kajstura, Jan
AU - Anversa, Piero
AU - Beltrami, Carlo A.
AU - Leri, Annarosa
PY - 2011/7
Y1 - 2011/7
N2 - Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21Cip1 and p16INK4a expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy.
AB - Currently, it is unknown whether defects in stem cell growth and differentiation contribute to myocardial aging and chronic heart failure (CHF), and whether a compartment of functional human cardiac stem cells (hCSCs) persists in the decompensated heart. To determine whether aging and CHF are critical determinants of the loss in growth reserve of the heart, the properties of hCSCs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent hCSCs. Chronological age was a major predictor of five biomarkers of hCSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21Cip1 and p16INK4a expression. CHF had similar consequences for hCSCs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent hCSCs may condition the evolution of the decompensated myopathy. A correlation was found previously between telomere length in circulating bone marrow cells and cardiovascular diseases, but that analysis was restricted to average telomere length in a cell population, neglecting the fact that telomere attrition does not occur uniformly in all cells. The present study provides the first demonstration that dysfunctional telomeres in hCSCs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of hCSCs and to sort young cells with potential therapeutic efficacy.
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U2 - 10.1016/j.ajpath.2011.03.036
DO - 10.1016/j.ajpath.2011.03.036
M3 - Article
C2 - 21703415
AN - SCOPUS:80052494147
SN - 0002-9440
VL - 179
SP - 349
EP - 366
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 1
ER -