title: Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery.
abstract: 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.
  
  
  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.affiliation: Department of Cardiovascular Sciences, Catholic University of the Sacred Heart, Rome, Italy (D.D'A., A.M.L., A.I., N.L., M.G., M. Manchi, A. Severino, F.G., G.B., A.M., C.S., G.L.D.M., C.C., A. Siracusano, L.O., M. Massetti, F.C.); and Departments of Anesthesia and Medicine, and Division of Cardiovascular Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA (D.D'A., R.K., S.H.S., P.G., A.L., P.A.).
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Amario
authors.forename: Antonio M
authors.initials: AM
authors.lastname: Leone
authors.forename: Antonio
authors.initials: A
authors.lastname: Iaconelli
authors.forename: Nicola
authors.initials: N
authors.lastname: Luciani
authors.forename: Mario
authors.initials: M
authors.lastname: Gaudino
authors.forename: Ramaswamy
authors.initials: R
authors.lastname: Kannappan
authors.forename: Melissa
authors.initials: M
authors.lastname: Manchi
authors.forename: Anna
authors.initials: A
authors.lastname: Severino
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Francesca
authors.initials: F
authors.lastname: Graziani
authors.forename: Gina
authors.initials: G
authors.lastname: Biasillo
authors.forename: Andrea
authors.initials: A
authors.lastname: Macchione
authors.forename: Costantino
authors.initials: C
authors.lastname: Smaldone
authors.forename: Giovanni Luigi
authors.initials: GL
authors.lastname: De Maria
authors.forename: Carlo
authors.initials: C
authors.lastname: Cellini
authors.forename: Andrea
authors.initials: A
authors.lastname: Siracusano
authors.forename: Lara
authors.initials: L
authors.lastname: Ottaviani
authors.forename: Massimo
authors.initials: M
authors.lastname: Massetti
authors.forename: Polina
authors.initials: P
authors.lastname: Goichberg
authors.forename: Annarosa
authors.initials: A
authors.lastname: Leri
authors.forename: Piero
authors.initials: P
authors.lastname: Anversa
authors.forename: Filippo
authors.initials: F
authors.lastname: Crea
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000097:blood; D049109:Cell Proliferation; D002478:Cells, Cultured; D001026:Coronary Artery Bypass; D016207:Cytokines / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D017228:Hepatocyte Growth Factor / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000097:blood / Q000473:pathology* / Q000601:surgery*; D009206:Myocardium / Q000473:pathology*; D011237:Predictive Value of Tests; D017526:Receptor, IGF Type 1 / Q000097:blood; D013234:Stem Cells / Q000473:pathology* / Q000648:ultrastructure; D019098:Telomerase / Q000502:physiology; D016615:Telomere / Q000648:ultrastructure; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
chemical_list: D015415:Biomarkers; D016207:Cytokines; D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor; D017526:Receptor, IGF Type 1; D019098:Telomerase
keywords: coronary artery disease; receptor, IGF type 1; stem cells; telomerase; telomere; ventricular remodeling