Cardiovascular diseases are the most common cause of death worldwide and their incidence is expected to increase further within the next decades. This high burden is largely attributed to the lack of significant cardiac regeneration in the adult heart, owing to the inability of cardiomyocytes to divide. In contrast, hearts of new-born mice and potentially human exhibit a remarkable capacity for cardiac muscle regeneration through compensatory proliferation of cardiomyocytes. Substantial efforts were already undertaken to decipher the molecular switches that distinguish the proliferating neonatal cardiomyocyte from the largely post-mitotic adult cardiomyocyte.
Nevertheless, these efforts mainly focused on protein coding genes and only few were identified to date that appear to control cardiac regeneration. Manipulation of those genes induces cardiomyocyte proliferation in vitro and to varying degrees cardiac regeneration in preclinical animal models. Clinical translation of these findings, however, is still entirely lacking. Thus, pharmacological stimulation of endogenous cardiac regeneration of the injured heart, e.g. after myocardial infarction, remains a distant goal which requires further tremendous research efforts.
With the development of next generation sequencing technologies, it became evident that large proportions of the mammalian genomes are transcribed into non-(protein)-coding RNAs (ncRNA), including microRNAs, long-non-coding RNAs (lncRNA) and the recently discovered circular RNAs (circRNA). It is now undisputed that the various types of ncRNA are functional molecules which can act as master regulators of gene expression. Therefore, they may have crucial functions in controlling virtually all biological processes including cardiac regeneration.
Importantly, ncRNAs represent therapeutic target structures. For example, derailed expression of a given ncRNA can be repressed by anti-sense oligonucleotides which then block the function or induce degradation of the targeted RNA molecule. By contrast, synthetic ncRNA mimics can be used to restore the function of an endogenous ncRNA. Indeed, these approaches have been already successfully applied in different disease settings in vitro and in vivo. Notably, several microRNA-based drugs are already under investigation in a number of clinical trials, including those for pathological heart conditions. However, concerning cardiac diseases, all current drugs are designed to slow down or halt the progression of an already existing heart condition, but not at curing them through unlocking endogenous cardiac regeneration.
This Research Topic welcomes submissions on current in vitro and in vivo approaches aiming at inducing cardiac regeneration by modulation of ncRNA expression. Original articles will be preferred but a small number of review articles and methodological articles can be included. Thus, this Research Topic aims to provide a comprehensive overview of current cardiac regenerative strategies which may include, but is not restricted to research in neonatal heart regeneration, in regeneration in the diseased adult heart, in modelling cardiac regeneration using state of the art in vitro platforms, and also research that addresses the interplay of different cardiac cell-types in regenerative processes.
Topic Editors Dr. Christian Bär and Dr. Reinier Boon are co-inventors on patent applications describing the use of non-coding RNAs as therapeutic targets for the treatment of cardiovascular diseases. Dr. Bernhard Haubner declares no conflicts of interest with regards to the Research Topic subject.
Cardiovascular diseases are the most common cause of death worldwide and their incidence is expected to increase further within the next decades. This high burden is largely attributed to the lack of significant cardiac regeneration in the adult heart, owing to the inability of cardiomyocytes to divide. In contrast, hearts of new-born mice and potentially human exhibit a remarkable capacity for cardiac muscle regeneration through compensatory proliferation of cardiomyocytes. Substantial efforts were already undertaken to decipher the molecular switches that distinguish the proliferating neonatal cardiomyocyte from the largely post-mitotic adult cardiomyocyte.
Nevertheless, these efforts mainly focused on protein coding genes and only few were identified to date that appear to control cardiac regeneration. Manipulation of those genes induces cardiomyocyte proliferation in vitro and to varying degrees cardiac regeneration in preclinical animal models. Clinical translation of these findings, however, is still entirely lacking. Thus, pharmacological stimulation of endogenous cardiac regeneration of the injured heart, e.g. after myocardial infarction, remains a distant goal which requires further tremendous research efforts.
With the development of next generation sequencing technologies, it became evident that large proportions of the mammalian genomes are transcribed into non-(protein)-coding RNAs (ncRNA), including microRNAs, long-non-coding RNAs (lncRNA) and the recently discovered circular RNAs (circRNA). It is now undisputed that the various types of ncRNA are functional molecules which can act as master regulators of gene expression. Therefore, they may have crucial functions in controlling virtually all biological processes including cardiac regeneration.
Importantly, ncRNAs represent therapeutic target structures. For example, derailed expression of a given ncRNA can be repressed by anti-sense oligonucleotides which then block the function or induce degradation of the targeted RNA molecule. By contrast, synthetic ncRNA mimics can be used to restore the function of an endogenous ncRNA. Indeed, these approaches have been already successfully applied in different disease settings in vitro and in vivo. Notably, several microRNA-based drugs are already under investigation in a number of clinical trials, including those for pathological heart conditions. However, concerning cardiac diseases, all current drugs are designed to slow down or halt the progression of an already existing heart condition, but not at curing them through unlocking endogenous cardiac regeneration.
This Research Topic welcomes submissions on current in vitro and in vivo approaches aiming at inducing cardiac regeneration by modulation of ncRNA expression. Original articles will be preferred but a small number of review articles and methodological articles can be included. Thus, this Research Topic aims to provide a comprehensive overview of current cardiac regenerative strategies which may include, but is not restricted to research in neonatal heart regeneration, in regeneration in the diseased adult heart, in modelling cardiac regeneration using state of the art in vitro platforms, and also research that addresses the interplay of different cardiac cell-types in regenerative processes.
Topic Editors Dr. Christian Bär and Dr. Reinier Boon are co-inventors on patent applications describing the use of non-coding RNAs as therapeutic targets for the treatment of cardiovascular diseases. Dr. Bernhard Haubner declares no conflicts of interest with regards to the Research Topic subject.
