Heart Care Info - Heart Disease Prevention & Treatment

Effects of age and heart failure on human cardiac stem cell function.

D Cesselli, AP Beltrami, F D'Aurizio... - The American journal ..., 2011 - 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 (h CSCs) persists in the decompensated heart. To determine whether aging ...

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 (h CS Cs) 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 h CS Cs were evaluated in 18 control and 23 explanted hearts. Age and CHF showed a progressive decrease in functionally competent h CS Cs. Chronological age was a major predictor of five biomarkers of h CSC senescence: telomeric shortening, attenuated telomerase activity, telomere dysfunction-induced foci, and p21(Cip1) and p16(INK4a) expression. CHF had similar consequences for h CS Cs, suggesting that defects in the balance between cardiomyocyte mass and the pool of nonsenescent h CS Cs 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 h CS Cs are biomarkers of aging and heart failure. The biomarkers of cellular senescence identified here can be used to define the birth date of h CS Cs and to sort young cells with potential therapeutic efficacy.