Effects of Age and Heart Failure on Human Cardiac Stem Cell Function

被引：150

作者：

Cesselli, Daniela ^{[1
]}

Beltrami, Antonio P. ^{[1
]}

D'Aurizio, Federica ^{[1
]}

Marcon, Patrizia ^{[1
]}

Bergamin, Natascha ^{[1
]}

Toffoletto, Barbara ^{[1
]}

Pandolfi, Maura ^{[1
]}

Puppato, Elisa ^{[1
]}

Marino, Laura ^{[3
]}

Signore, Sergio ^{[4
,5
]}

Livi, Ugolino ^{[2
]}

Verardo, Roberto ^{[6
]}

Piazza, Silvan ^{[6
]}

Marchionni, Luigi ^{[7
]}

Fiorini, Claudia ^{[8
]}

Schneider, Claudio ^{[6
]}

Hosoda, Toru ^{[4
,5
]}

Rota, Marcello ^{[4
,5
]}

Kajstura, Jan ^{[4
,5
]}

Anversa, Piero ^{[4
,5
]}

Beltrami, Carlo A.

Leri, Annarosa ^{[4
,5
]}

机构：

[1] Udine Med Sch, Ctr Regenerat Med, I-33100 Udine, Italy

[2] Udine Med Sch, Dept Cardiac Surg, I-33100 Udine, Italy

[3] Naples Second Med Sch, Dept Expt Med, Naples, Italy

[4] Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Anesthesia & Med, Boston, MA 02115 USA

[5] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Cardiovasc Med, Boston, MA 02115 USA

[6] Natl Biotechnol Lab LNCIB, Trieste, Italy

[7] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA

[8] Albert Einstein Coll Med, Montefiore Med Ctr, New York, NY USA

来源：

AMERICAN JOURNAL OF PATHOLOGY | 2011年 / 179卷 / 01期

关键词：

TELOMERE LENGTH; SENESCENCE; ACTIVATION; MOUSE; MICE; CARDIOMYOGENESIS; DISCOVERY; DISEASE; END;

D O I：

10.1016/j.ajpath.2011.03.036

中图分类号：

R36 [病理学];

学科分类号：

100103 [病原生物学];

摘要：

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 p21(cip1) and p16(INK4a) 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. (Am J Pathol 2011, 179:349-364. DOI: 10.1016/j.ajpath.2011.03.036)

引用

页码：349 / 366

页数：18

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