Effects of Cardiac Stem Cell on Postinfarction Arrhythmogenic Substrate

Autor: Ángel Arenal, Gonzalo R. Ríos-Muñoz, Alejandro Carta-Bergaz, Pablo M. Ruiz-Hernández, Esther Pérez-David, Verónica Crisóstomo, Gerard Loughlin, Ricardo Sanz-Ruiz, Javier Fernández-Portales, Alejandra Acosta, Claudia Báez-Díaz, Virginia Blanco-Blázquez, María J. Ledesma-Carbayo, Miriam Pareja, María E. Fernández-Santos, Francisco M. Sánchez-Margallo, Javier G. Casado, Francisco Fernández-Avilés
Přispěvatelé: European Commission, Ministerio de Ciencia e Innovación (España)
Rok vydání: 2022
Předmět:
Zdroj: International Journal of Molecular Sciences; Volume 23; Issue 24; Pages: 16211
ISSN: 1422-0067
Popis: This article belongs to the Special Issue New Insights into Cardiovascular Diseases in Basic Research. Clinical data suggest that cardiosphere-derived cells (CDCs) could modify post-infarction scar and ventricular remodeling and reduce the incidence of ventricular tachycardia (VT). This paper assesses the effect of CDCs on VT substrate in a pig model of postinfarction monomorphic VT. We studied the effect of CDCs on the electrophysiological properties and histological structure of dense scar and heterogeneous tissue (HT). Optical mapping and histological evaluation were performed 16 weeks after the induction of a myocardial infarction by transient occlusion of the left anterior descending (LAD) artery in 21 pigs. Four weeks after LAD occlusion, pigs were randomized to receive intracoronary plus trans-myocardial CDCs (IC+TM group, n: 10) or to a control group. Optical mapping (OM) showed an action potential duration (APD) gradient between HT and normal tissue in both groups. CDCs increased conduction velocity (53 ± 5 vs. 45 ± 6 cm/s, p < 0.01), prolonged APD (280 ± 30 ms vs. 220 ± 40 ms, p < 0.01) and decreased APD dispersion in the HT. During OM, a VT was induced in one and seven of the IC+TM and control hearts (p = 0.03), respectively; five of these VTs had their critical isthmus located in intra-scar HT found adjacent to the coronary arteries. Histological evaluation of HT revealed less fibrosis (p < 0.01), lower density of myofibroblasts (p = 0.001), and higher density of connexin-43 in the IC+TM group. Scar and left ventricular volumes did not show differences between groups. Allogeneic CDCs early after myocardial infarction can modify the structure and electrophysiology of post-infarction scar. These findings pave the way for novel therapeutic properties of CDCs. This study was funded by the National Fund for Health Research (Fondo de Investigación Sanitaria) from the Spanish Ministry of Science and Innovation, Spain [PI10/02771, TIN2007-68048-C02-01, TIN2007-68048-C02-02, PI13-01882, PI13-00903, PI13/02858, IJCI-2014-22178, TEC2010-21619-C04-03]; the Cooperative Cardiovascular Disease Research Network RIC [RD12/0042/0001]; the Instituto de Salud Carlos III, Madrid, Spain (PI18/01895 and DTS21/00064); Red de Terapia Celular from the Instituto de Salud Carlos III, Madrid, Spain (RD16/0011/0029, RD12/0019/0021); the European Union's H2020 Program under grant agreement No. 874827 (BRAVE); and Ricors-Red de Investigación Cooperativa Orientada a Resultados en Salud RICORS TERAV (RD21.0017.0002). Proyecto de Investigación translacional 2019 de la Sociedad Española de Cardiología (Caracterización del sustrato arrítmico epicárdico en un modelo porcino de taquicardia ventricular post-infarto).
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje