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Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart

Adams, E, McCloy, R, Jordan, A, Falconer, K and Dykes, IM (2021) Direct Reprogramming of Cardiac Fibroblasts to Repair the Injured Heart. Journal of Cardiovascular Development and Disease, 8 (7). ISSN 2308-3425

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Abstract

Coronary heart disease is a leading cause of mortality and morbidity. Those that survive acute myocardial infarction are at significant risk of subsequent heart failure due to fibrotic remodelling of the infarcted myocardium. By applying knowledge from the study of embryonic cardiovascular development, modern medicine offers hope for treatment of this condition through regeneration of the myocardium by direct reprogramming of fibrotic scar tissue. Here, we will review mechanisms of cell fate specification leading to the generation of cardiovascular cell types in the embryo and use this as a framework in which to understand direct reprogramming. Driving expression of a network of transcription factors, micro RNA or small molecule epigenetic modifiers can reverse epigenetic silencing, reverting differentiated cells to a state of induced pluripotency. The pluripotent state can be bypassed by direct reprogramming in which one differentiated cell type can be transdifferentiated into another. Transdifferentiating cardiac fibroblasts to cardiomyocytes requires a network of transcription factors similar to that observed in embryonic multipotent cardiac progenitors. There is some flexibility in the composition of this network. These studies raise the possibility that the failing heart could one day be regenerated by directly reprogramming cardiac fibroblasts within post-infarct scar tissue.

Item Type: Article
Subjects: Q Science > QP Physiology
R Medicine > R Medicine (General)
R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RD Surgery
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: MDPI
Date Deposited: 05 Jul 2021 09:37
Last Modified: 05 Jul 2021 09:37
DOI or Identification number: 10.3390/jcdd8070072
URI: https://researchonline.ljmu.ac.uk/id/eprint/15206

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