Financiado en parte por Boehringer Ingelheim Fonds
Decreased creatine kinase is linked to diastolic dysfunction in rats with right heart failure induced by pulmonary artery hypertension
Fowler ED, Benoist D, Drinkhill MJ, Stones R, Helmes M, Wüst RC, Stienen GJ, Steele DS, White E
Journal of molecular and cellular cardiology · 45 citas
Etiquetas de revisión
Vínculos de autores con la industriaFinanciado por la industriaDatos neutrales que nuestra revisión registró sobre cómo se hizo este estudio. Describen el método, nunca si nos gusta el resultado.
Cómo se estudió
- Diseño
- Estudio en animales (clasificado por nuestro filtro de IA)
- Estudiado en
- Animales
- Resultado principal
- Marcadores de salud y funcionamiento
Quién lo pagó
- Financiación
- Financiado por la industria
- Organización sin fines de lucro
- British Heart Foundation
- Universidad u hospital
- University of Leeds
- Empresa
- Boehringer Ingelheim Fonds
- Autores
- Al menos un autor declara un vínculo económico con la industria
- Subvenciones
- British Heart Foundation (RG/11/10/28924); British Heart Foundation (PG/13/3/29924)
Según 3 financiadores declarados y la declaración de financiación del texto completo.
Publicación
- Publicado
- 2015-06-24 · J Mol Cell Cardiol · vol. 86 · págs. 1–8
- Editorial
- Elsevier BV
- Citado
- 49 citas · más que el 91% de estudios similares · 2.6× el promedio de su campo
- Impacto
- Entre el 10 % más citado de su campo
- Referencias
- 47 trabajos
- Acceso
- Acceso abierto (revista híbrida) · CC-BY
- Áreas de investigación
- Cardiovascular Effects of Exercise · Pulmonary Hypertension Research and Treatments · Cardiomyopathy and Myosin Studies
- Palabras clave
- Internal medicine, Sarcomere, Creatine kinase, Cardiology, Diastole, Heart failure, Pulmonary artery, Medicine, Myocyte, Ventricle, Pulmonary hypertension, Creatine, Endocrinology, Blood pressure
- MeSH
- sarcomeres, myocardium, pulmonary artery, myocytes, cardiac, animals, humans, rats, hypertension, pulmonary, ventricular dysfunction, right, calcium, creatine kinase, adenosine triphosphate, diastole, heart failure
9 autores
- Ewan Douglas Fowler🇬🇧University of Leeds
- David Benoîst🇬🇧🇫🇷University of Leeds; Université de Bordeaux; Inserm; Electrophysiology and Heart Modeling Institute; Centre de Recherche Cardio-Thoracique de Bordeaux
- Mark J. Drinkhill🇬🇧University of Leeds
- Rachel Stones🇬🇧University of Leeds
- Michiel Helmes🇺🇸🇳🇱Intralytix (United States); Amsterdam Cardiovascular Sciences; Amsterdam UMC Location Vrije Universiteit Amsterdam
- Rob C. I. Wüst🇳🇱Amsterdam Cardiovascular Sciences; Amsterdam UMC Location Vrije Universiteit Amsterdam
- Ger J.M. Stienen🇳🇱Amsterdam Cardiovascular Sciences; Amsterdam UMC Location Vrije Universiteit Amsterdam
- Derek S. Steele🇬🇧University of Leeds
- Ed White🇬🇧 · autor de correspondenciaUniversity of Leeds
Resumen
El texto original del estudio, en el idioma en que se publicó.
Our objective was to investigate the role of creatine kinase in the contractile dysfunction of right ventricular failure caused by pulmonary artery hypertension. Pulmonary artery hypertension and right ventricular failure were induced in rats by monocrotaline and compared to saline-injected control animals. In vivo right ventricular diastolic pressure-volume relationships were measured in anesthetized animals; diastolic force-length relationships in single enzymatically dissociated myocytes and myocardial creatine kinase levels by Western blot. We observed diastolic dysfunction in right ventricular failure indicated by significantly steeper diastolic pressure-volume relationships in vivo and diastolic force-length relationships in single myocytes. There was a significant reduction in creatine kinase protein expression in failing right ventricle. Dysfunction also manifested as a shorter diastolic sarcomere length in failing myocytes. This was associated with a Ca(2+)-independent mechanism that was sensitive to cross-bridge cycling inhibition. In saponin-skinned failing myocytes, addition of exogenous creatine kinase significantly lengthened sarcomeres, while in intact healthy myocytes, inhibition of creatine kinase significantly shortened sarcomeres. Creatine kinase inhibition also changed the relatively flat contraction amplitude-stimulation frequency relationship of healthy myocytes into a steeply negative, failing phenotype. Decreased creatine kinase expression leads to diastolic dysfunction. We propose that this is via local reduction in ATP:ADP ratio and thus to Ca(2+)-independent force production and diastolic sarcomere shortening. Creatine kinase inhibition also mimics a definitive characteristic of heart failure, the inability to respond to increased demand. Novel therapies for pulmonary artery hypertension are needed. Our data suggest that cardiac energetics would be a potential ventricular therapeutic target.
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