Submit Manuscript  

Article Details


Targeting the Cardiomyocyte Cell Cycle for Heart Regeneration

[ Vol. 20 , Issue. 2 ]

Author(s):

Paola Locatelli*, Carlos Sebastian Gimenez, Martin Uranga Vega, Alberto Crottogini and Mariano Nicolas Belaich   Pages 241 - 254 ( 14 )

Abstract:


Adult mammalian cardiomyocytes (CMs) exhibit limited proliferative capacity, as cell cycle activity leads to an increase in DNA content, but mitosis and cytokinesis are infrequent. This makes the heart highly inefficient in replacing with neoformed cardiomyocytes lost contractile cells as occurs in diseases such as myocardial infarction and dilated cardiomyopathy. Regenerative therapies based on the implant of stem cells of diverse origin do not warrant engraftment and electromechanical connection of the new cells with the resident ones, a fundamental condition to restore the physiology of the cardiac syncytium. Consequently, there is a growing interest in identifying factors playing relevant roles in the regulation of the CM cell cycle to be targeted in order to induce the resident cardiomyocytes to divide into daughter cells and thus achieve myocardial regeneration with preservation of physiologic syncytial performance. Despite the scientific progress achieved over the last decades, many questions remain unanswered, including how cardiomyocyte proliferation is regulated during heart development in gestation and neonatal life. This can reveal unknown cell cycle regulation mechanisms and molecules that may be manipulated to achieve cardiac self-regeneration. We hereby revise updated data on CM cell cycle regulation, participating molecules and pathways recently linked with the cell cycle, as well as experimental therapies involving them.

Keywords:

Cell cycle, cardiomyocyte, heart, mitosis, INK4, Cip/Kip.

Affiliation:

Laboratorio de Regeneracion Cardiovascular, Instituto de Medicina Traslacional, Trasplante y Bioingenieria (IMETTYB), Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) - Universidad Favaloro, Solis 453, Buenos Aires, Laboratorio de Regeneracion Cardiovascular, Instituto de Medicina Traslacional, Trasplante y Bioingenieria (IMETTYB), Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) - Universidad Favaloro, Solis 453, Buenos Aires, Laboratorio de Regeneracion Cardiovascular, Instituto de Medicina Traslacional, Trasplante y Bioingenieria (IMETTYB), Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) - Universidad Favaloro, Solis 453, Buenos Aires, Laboratorio de Regeneracion Cardiovascular, Instituto de Medicina Traslacional, Trasplante y Bioingenieria (IMETTYB), Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) - Universidad Favaloro, Solis 453, Buenos Aires, Laboratorio de Ingenieria Genetica y Biologia Celular y Molecular, Consejo Nacional de Investigaciones Científicas y Tecnicas (CONICET) - Universidad Nacional de Quilmes (UNQ), Roque Saenz Pena 352, Bernal, Buenos Aires



Read Full-Text article