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Structural and functional cardiac profile after prolonged duration of mechanical unloading: potential implications for myocardial recovery.
Castillero, Estibaliz; Ali, Ziad A; Akashi, Hirokazu; Giangreco, Nicholas; Wang, Catherine; Stöhr, Eric J; Ji, Ruping; Zhang, Xiaokan; Kheysin, Nathaniel; Park, Joo-Eun S; Hegde, Sheetal; Patel, Sanatkumar; Stein, Samantha; Cuenca, Carlos; Leung, Diana; Homma, Shunichi; Tatonetti, Nicholas P; Topkara, Veli K; Takeda, Koji; Colombo, Paolo C; Naka, Yoshifumi; Sweeney, H Lee; Schulze, P Christian; George, Isaac.
Afiliación
  • Castillero E; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Ali ZA; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Akashi H; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Giangreco N; Department of Biomedical Informatics, Systems Biology, Institute for Genomic Medicine, Data Science Institute, Columbia University , New York, New York.
  • Wang C; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Stöhr EJ; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Ji R; School of Sport and Health Sciences, Cardiff Metropolitan University , Cardiff , United Kingdom.
  • Zhang X; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Kheysin N; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Park JS; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Hegde S; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Patel S; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Stein S; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Cuenca C; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Leung D; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Homma S; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Tatonetti NP; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Topkara VK; Department of Biomedical Informatics, Systems Biology, Institute for Genomic Medicine, Data Science Institute, Columbia University , New York, New York.
  • Takeda K; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Colombo PC; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Naka Y; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Sweeney HL; Division of Cardiothoracic Surgery, College of Physicians and Surgeons of Columbia University , New York, New York.
  • Schulze PC; Department of Pharmacology, University of Florida , Gainesville, Florida.
  • George I; Division of Cardiology, College of Physicians and Surgeons of Columbia University , New York, New York.
Am J Physiol Heart Circ Physiol ; 315(5): H1463-H1476, 2018 11 01.
Article en En | MEDLINE | ID: mdl-30141986
ABSTRACT
Clinical and experimental studies have suggested that the duration of left ventricular assist device (LVAD) support may affect remodeling of the failing heart. We aimed to 1) characterize the changes in Ca2+/calmodulin-dependent protein kinase type-IIδ (CaMKIIδ), growth signaling, structural proteins, fibrosis, apoptosis, and gene expression before and after LVAD support and 2) assess whether the duration of support correlated with improvement or worsening of reverse remodeling. Left ventricular apex tissue and serum pairs were collected in patients with dilated cardiomyopathy ( n = 25, 23 men and 2 women) at LVAD implantation and after LVAD support at cardiac transplantation/LVAD explantation. Normal cardiac tissue was obtained from healthy hearts ( n = 4) and normal serum from age-matched control hearts ( n = 4). The duration of LVAD support ranged from 48 to 1,170 days (median duration 270 days). LVAD support was associated with CaMKIIδ activation, increased nuclear myocyte enhancer factor 2, sustained histone deacetylase-4 phosphorylation, increased circulating and cardiac myostatin (MSTN) and MSTN signaling mediated by SMAD2, ongoing structural protein dysregulation and sustained fibrosis and apoptosis (all P < 0.05). Increased CaMKIIδ phosphorylation, nuclear myocyte enhancer factor 2, and cardiac MSTN significantly correlated with the duration of support. Phosphorylation of SMAD2 and apoptosis decreased with a shorter duration of LVAD support but increased with a longer duration of LVAD support. Further study is needed to define the optimal duration of LVAD support in patients with dilated cardiomyopathy. NEW & NOTEWORTHY A long duration of left ventricular assist device support may be detrimental for myocardial recovery, based on myocardial tissue experiments in patients with prolonged support showing significantly worsened activation of Ca2+/calmodulin-dependent protein kinase-IIδ, increased nuclear myocyte enhancer factor 2, increased myostatin and its signaling by SMAD2, and apoptosis as well as sustained histone deacetylase-4 phosphorylation, structural protein dysregulation, and fibrosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Corazón Auxiliar / Función Ventricular Izquierda / Insuficiencia Cardíaca / Ventrículos Cardíacos / Miocardio Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2018 Tipo del documento: Article
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cardiomiopatía Dilatada / Corazón Auxiliar / Función Ventricular Izquierda / Insuficiencia Cardíaca / Ventrículos Cardíacos / Miocardio Tipo de estudio: Etiology_studies / Observational_studies / Risk_factors_studies Límite: Female / Humans / Male / Middle aged Idioma: En Revista: Am J Physiol Heart Circ Physiol Asunto de la revista: CARDIOLOGIA / FISIOLOGIA Año: 2018 Tipo del documento: Article