Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery

Domenico D'Amario, Antonio M. Leone, Amerigo Iaconelli, Nicola Luciani, Mario Fulvio Luigi Gaudino, Ramaswamy Kannappan, Melissa Manchi, Anna Severino, Sang Hun Shin, Francesca Graziani, Gina Biasillo, Andrea Macchione, Costantino Smaldone, Giovanni Luigi De Maria, Carlo Cellini, Andrea Siracusano, Lara Ottaviani, Massimo Massetti, Polina Goichberg, Annarosa LeriPiero Anversa, Filippo Crea

Risultato della ricerca: Contributo in rivistaArticolo in rivista

24 Citazioni (Scopus)


BACKGROUND: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population. METHODS AND RESULTS: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction. CONCLUSIONS: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.
Lingua originaleEnglish
pagine (da-a)157-172
Numero di pagine16
Stato di pubblicazionePubblicato - 2014


  • coronary artery disease


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