Dual roles of telomerase in cardiac protection and repair.
Together, the limited capacity for regenerative growth in cardiac muscle after injury and the prevalence of ongoing sporadic cell death due to apoptosis in chronic heart failure states pose one of the paramount challenges in heart failure therapeutics. In adults, the unique self-renewal potential of progenitor/stem cells is associated with telomerase reverse transcriptase (TERT), an RNA-dependent DNA polymerase that maintains the lariat-like loop capping chromosome ends. We have identified telomere uncapping, mediated by down-regulation of telomere repeat-binding factor 2 (TRF2) as a novel trigger of cell death in human dilated cardiomyopathy. Conversely, we identified a residual TERT+ population in adult myocardium, as a potential source of cardiac progenitor cells. Residual TERT expression was localized to cells expressing stem cell antigen 1 (Sca1). Cardiac-resident Sca1+ cells lack haematopoietic stem cell markers and transcripts for cardiac structural genes, yet express many cardiogenic transcription factors. If given intravenously to mice just after ischemia-reperfusion injury, cardiac Sca1+ cells home selectively to injured myocardium and differentiate spontaneously in situ.
Schneider
Michael D
MD
Center for Cardiovascular Development, Department of Medicne, Baylor College of Medicine, One Baylor Plaza, Room 506D, Houston, TX 77030, USA.
D000818:Animals; D002454:Cell Differentiation; D006321:Heart / Q000502:physiology*; D006331:Heart Diseases / Q000473:pathology; D006801:Humans; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D019098:Telomerase / Q000378:metabolism / Q000502:physiology*
D019098:Telomerase