Abstract 3214: Elevated c-kit and nkx2.5 Expression in Human Cardiomyopathy Hearts: Suggestive of Fetal Gene Re-programming
Background: Cardiomyocytes experiencing hemodynamic or metabolic stress may undergo fetal gene reprogramming to upregulate expression of transcription factors, proteins, and uncommitted progenitor cells. In this way, cardiomyocytes compensate to increase cardiac efficiency. C-kit(CD117) is a cytokine receptor expressed on cardiac progenitors which assist in cell survival and proliferation. We hypothesize that human cardiomyopathic heart tissue from right atrium reverses to the fetal gene program with age by increasing c-kit and nkx2.5 expression.
Methods: Samples from healthy (n=17) or cardiomyopathic (n=4) right atrial appendages were obtained, ranging in weights from 110 – 685 mg. Donor ages ranged from 2 weeks-14 years.
Results: In children above 12 years, there was significantly higher c-kit, nkx2.5, and ki67 expression in cardiomyopathy compared to healthy (Table-1⇓). Ki67 expression declined significantly with age (15±0.1 verses 5±0.2) in healthy compared to cardiomyopathy. Isolated cardiac progenitor cell proliferation from RAA significantly outperformed ventricular biopsies in cardiomyopathy patients (114,000±7,000 to 31,500±10,500 respectively).
Conclusion: Positive c-kit, nkx2.5, and ckit/nkx2.5 coexpression was inversely proportional between healthy and cardiomyopathic biopsies with increasing age, suggesting a reversal to the fetal gene program.