TITIN DOWNREGULATION AFFECTS CARDIOMYOCYTES PROLIFERATION

A recent investigation, focused on the potential of specific miRNAs to augment CM proliferation, has unveiled that this phenomenon arises from the cumulative impact on multiple mRNA targets within the cells (4). This comprehensive analysis of genes downregulated by these miRNAs has demonstrated a noteworthy enrichment in genes associated with categories such as 'skeletal and muscular system development and function' and 'cellular assembly and organization.' Among these genes is TTN, a pivotal player. Notably, targeted downregulation of these genes has the potential to independently induce CM proliferation. In humans, it is well-established that TTNtv represent a preeminent genetic ethology of DCM, with their pathogenicity primarily attributed to haploinsufficiency mechanisms(75). The aim of this study is to probe the repercussions of reducing TTN levels, particularly with regard to cardiac myocyte turnover and proliferative dynamics, and if these replicative abnormalities could be a causative association with TTNtv-DCM. To induce a targeted reduction in TTN expression, we have employed a precise strategy involving the administration of TTN-specific siRNA/shRNA respectively in vitro and in vivo models. This approach enabled us to comprehensively evaluate cardiac phenotypic alterations, conduct an in-depth examination of CM structural changes, and explore the proliferative capacities of the cells under regulated TTN downregulation.

A recent investigation, focused on the potential of specific miRNAs to augment CM proliferation, has unveiled that this phenomenon arises from the cumulative impact on multiple mRNA targets within the cells (4). This comprehensive analysis of genes downregulated by these miRNAs has demonstrated a noteworthy enrichment in genes associated with categories such as 'skeletal and muscular system development and function' and 'cellular assembly and organization.' Among these genes is TTN, a pivotal player. Notably, targeted downregulation of these genes has the potential to independently induce CM proliferation. In humans, it is well-established that TTNtv represent a preeminent genetic ethology of DCM, with their pathogenicity primarily attributed to haploinsufficiency mechanisms(75). The aim of this study is to probe the repercussions of reducing TTN levels, particularly with regard to cardiac myocyte turnover and proliferative dynamics, and if these replicative abnormalities could be a causative association with TTNtv-DCM. To induce a targeted reduction in TTN expression, we have employed a precise strategy involving the administration of TTN-specific siRNA/shRNA respectively in vitro and in vivo models. This approach enabled us to comprehensively evaluate cardiac phenotypic alterations, conduct an in-depth examination of CM structural changes, and explore the proliferative capacities of the cells under regulated TTN downregulation.