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Reassessing the Mechanisms of PLN-R14del Cardiomyopathy: From Calcium Dysregulation to S/ER Malformation.
Stege, Nienke M; de Boer, Rudolf A; Makarewich, Catherine A; van der Meer, Peter; Silljé, Herman H W.
Afiliação
  • Stege NM; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
  • de Boer RA; Erasmus Medical Center, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, the Netherlands.
  • Makarewich CA; Division of Molecular Cardiovascular Biology of the Heart Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, USA.
  • van der Meer P; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, Ohio, USA.
  • Silljé HHW; Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
JACC Basic Transl Sci ; 9(8): 1041-1052, 2024 Aug.
Article em En | MEDLINE | ID: mdl-39297138
ABSTRACT
The phospholamban (PLN) pathogenic gene variant, p.Arg14del (PLN-R14del), can lead to dilated and arrhythmogenic cardiomyopathy, resulting in heart failure. PLN-R14del cardiomyopathy has been conceptualized as a disease caused by sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) superinhibition. However, recent studies raised controversy regarding the effect of PLN-R14del on SERCA activity and revealed a prominent role for abnormal PLN protein distribution and sarco/endoplasmic reticulum disorganization as underlying disease mechanism. Strategies targeting sarco/endoplasmic reticulum malformation may, therefore, prove more effective than SERCA activity modulation. This review reassesses the disease mechanisms of PLN-R14del cardiomyopathy and emphasizes the importance of dissecting the underlying molecular mechanisms to uncover targets for innovative treatments.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Basic Transl Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Revista: JACC Basic Transl Sci Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda País de publicação: Estados Unidos