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.
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.
Authors: Paul J R Barton; Leanne E Felkin; Emma J Birks; Martin E Cullen; Nicholas R Banner; Suzanne Grindle; Jennifer L Hall; Leslie W Miller; Magdi H Yacoub Journal: Circulation Date: 2005-08-30 Impact factor: 29.690
Authors: L Bolognese; G Cerisano; P Buonamici; A Santini; G M Santoro; D Antoniucci; P F Fazzini Journal: Circulation Date: 1997-11-18 Impact factor: 29.690
Authors: Axel Linke; Patrick Müller; Daria Nurzynska; Claudia Casarsa; Daniele Torella; Angelo Nascimbene; Clotilde Castaldo; Stefano Cascapera; Michael Böhm; Federico Quaini; Konrad Urbanek; Annarosa Leri; Thomas H Hintze; Jan Kajstura; Piero Anversa Journal: Proc Natl Acad Sci U S A Date: 2005-06-10 Impact factor: 11.205
Authors: Marcello Rota; Nicole LeCapitaine; Toru Hosoda; Alessandro Boni; Antonella De Angelis; Maria Elena Padin-Iruegas; Grazia Esposito; Serena Vitale; Konrad Urbanek; Claudia Casarsa; Marco Giorgio; Thomas F Lüscher; Pier Giuseppe Pelicci; Piero Anversa; Annarosa Leri; Jan Kajstura Journal: Circ Res Date: 2006-06-08 Impact factor: 17.367
Authors: M A Pfeffer; E Braunwald; L A Moyé; L Basta; E J Brown; T E Cuddy; B R Davis; E M Geltman; S Goldman; G C Flaker Journal: N Engl J Med Date: 1992-09-03 Impact factor: 91.245
Authors: S Fazio; D Sabatini; B Capaldo; C Vigorito; A Giordano; R Guida; F Pardo; B Biondi; L Saccà Journal: N Engl J Med Date: 1996-03-28 Impact factor: 91.245
Authors: Collin Matsumoto; Yan Jiang; Jacqueline Emathinger; Pearl Quijada; Nathalie Nguyen; Andrea De La Torre; Maryam Moshref; Jonathan Nguyen; Aimee B Levinson; Minyoung Shin; Mark A Sussman; Nirmala Hariharan Journal: Stem Cells Date: 2018-02-25 Impact factor: 6.277
Authors: Brian J Page; Michael D Banas; Gen Suzuki; Brian R Weil; Rebeccah F Young; James A Fallavollita; Beth A Palka; John M Canty Journal: J Am Coll Cardiol Date: 2015-02-24 Impact factor: 24.094