2026-07-16T11:01:20Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/275822026-07-10T00:17:32Zcom_20.500.12105_19586com_20.500.12105_2202col_20.500.12105_19587

00925njm 22002777a 4500 dc Pricolo, Maria Rosaria author López-Unzu, Miguel A author Vicente, Natalia author Morales-López, Cristina author Huerta-López, Carla author Pérez-Franco, Wendy author Dumitru, Andra C author Peña-Peña, Jorge author Espinosa, Francisco M author Sanchez, Mateo I author Garcia, Ricardo author Silva-Rojas, Roberto author Torres, Miguel author Herrero-Galán, Elías author Alegre-Cebollada, Jorge author 2026-05-15 Adult mammalian hearts have limited regenerative capacity due to the inability of cardiomyocytes to proliferate, a major clinical hurdle in contemporary cardiology. The presence of highly organized, contractile sarcomeres has long been considered an impediment for cardiomyocyte division. Indeed, sarcomere disassembly is a crucial step to complete the cell cycle in the few situations where cardiomyocytes have been observed to proliferate. However, whether sarcomere disassembly can per se trigger cell cycle re-entry remains unknown, a possibility that we have tested here. In this study, we have engineered a system to induce sarcomere disassembly in living murine cardiomyocytes based on the specific cleavage of the structural protein titin by tobacco etch virus protease. Although isolated neonatal cardiomyocytes with disassembled sarcomeres remain viable and retain low-amplitude contractile activity, our results show no evidence of increased cardiomyocyte proliferation in targeted cells, as indicated by the analyses of markers of DNA synthesis and cytokinesis. We obtain equivalent results when titin is cleaved in cardiomyocytes stimulated with mitogenic factors in vitro and in the adult myocardium in vivo. These findings suggest that the removal of sarcomere structural barriers is necessary, but not sufficient, for cardiomyocyte proliferation, which implies that additional factors are required for cardiomyocytes to undergo cell division. J Biol Chem . 2026 May 15;302(7):113167 Journal of Biological Chemistry 42142587 https://hdl.handle.net/20.500.12105/27582 cardiac regeneration cardiomyocyte cell cycle proliferation sarcomere titin Titin cleavage in living cardiomyocytes induces sarcomere disassembly but does not trigger cell proliferation.