Abstract 12995: The Growth Properties of Cardiac Stem Cells are a Novel Biomarker of Left Ventricular remodeling and Outcome in Patients Undergoing Coronary Bypass Surgery at 1 Year Follow up
Rationale: The efficacy of bypass-surgery (CABG) in patients with ischemic cardiomyopathy is not easily predictable; pre-operative 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.
Objective: To document whether the growth kinetics of CSCs is a novel biomarker of clinical outcome after CABG.
Methods and Results: Population doubling time (PDT), telomere length, telomerase activity, and IGF-1 receptor (IGF-1R) expression were measured in CSCs isolated from 55 patients undergoing CABG. Additionally, the blood level of IGF-1, HGF, and VEGF were evaluated. The 4 variables of CSC growth were expressed as a function of the changes (Δ) in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, prior to, and 12 months after surgery. A high correlation was found between each of the indices of CSC function and the size and shape of the heart at 5 months and 1 year. A highly significant direct correlation between improvement of ejection fraction at FU and hCSC length of telomeres (p≤0.0001; R2 0.55), telomerase activity (p≤0.001; R2 0.54) and % of IGF1Rpos (p≤0.0001; R2 0.62) was observed as well as an inverse correlation with PDT (p≤0.0001; R2 0.71). Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. In this case, the high concentration of IGF-1 systemically pointed to the IGF-1-IGF-1R system as a major player in the adaptive response of the myocardium. HGF, a mediator of CSC migration, was also high in these patients preoperatively as did VEGF possibly reflecting vascular growth needed before CABG. Conversely, a decline in CSCs replicative potential was coupled with wall thinning, chamber dilation, reduction in ventricular mass-to-chamber volume ratio, decreased EF and low levels of IGF-1, HGF and VEGF.
Conclusions: The telomere-telomerase axis, PDT, and IGF-1R expression in CSCs, together with high circulating level of IGF-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following CABG.
- © 2013 by American Heart Association, Inc.