Transcription Profiles of Failing and Non-Failing Hearts after Two-Cycle RNA Amplification from Biopsy-Sized Samples

Abstract

Introduction: Recent findings report the potential for bone marrow(BM) or cardiac-derived stem and progenitor cell mobilization and differentiation to repair the infarcted myocardium. Following myocardial infarction (MI), there is an influx of inflammatory cells and secretion of cytokines, leading to cardiomyocyte death and ventricular remodeling. Mobilized c-Kitþ progenitor cells, either from the BM or cardiac niches, play a key role in maintenance of the number of myocytes in aging or postMI. We focused on determining the role of the c-Kit receptor in long term remodeling post-MI. Methods and Results: Functional repair in c-kit mutant (W/W) and littermate wild type (WT) mice post-MI was compared by evaluating in vivo left ventricular (LV) pressure-volume performance and pathology at 5 and 24 weeks post-MI. Evaluation of LV end-systolic and diastolic volume (ESV and EDV) showed a significant worsening of heart function and greater left ventricular dilatation at 5 and 24 weeks post-MI in W/W mice compared to WT (Figure 1). Similarly, the W/W sham and MI operated groups developed greater LV dilatation at 24 weeks when compared to W/W sham and MI mice at 5 weeks. Interestingly, WT sham and MI mice did not demonstrate any significant worsening of heart function at 24 weeks when compared to 5 weeks post-MI. Conclusion: This demonstrates the importance of c-Kit receptors in maintaining heart function post-MI and in aging. These findings provide further evidence indicating the presence of BMor cardiac residentderived stem progenitor cells in maintenance of myocardial health with age and post-injury. 133