Your browser doesn't support javascript.
loading
Impaired T cell IRE1α/XBP1 signaling directs inflammation in experimental heart failure with preserved ejection fraction.
Smolgovsky, Sasha; Bayer, Abraham L; Kaur, Kuljeet; Sanders, Erin; Aronovitz, Mark; Filipp, Mallory E; Thorp, Edward B; Schiattarella, Gabriele G; Hill, Joseph A; Blanton, Robert M; Cubillos-Ruiz, Juan R; Alcaide, Pilar.
Afiliación
  • Smolgovsky S; Department of Immunology, Tufts University, Boston, Massachusetts, USA.
  • Bayer AL; Department of Immunology, Tufts University, Boston, Massachusetts, USA.
  • Kaur K; Department of Immunology, Tufts University, Boston, Massachusetts, USA.
  • Sanders E; Department of Immunology, Tufts University, Boston, Massachusetts, USA.
  • Aronovitz M; Department of Immunology, Tufts University, Boston, Massachusetts, USA.
  • Filipp ME; Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
  • Thorp EB; Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA.
  • Schiattarella GG; Max Rubner Center for Cardiovascular Metabolic Renal Research (MRC), Deutsches Herzzentrum der Charité, Charité - Universitätsmedizin Berlin, Berlin, Germany.
  • Hill JA; DZHK (German Centre for Cardiovascular Research), Partner Site Berlin, Berlin, Germany.
  • Blanton RM; Translational Approaches in Heart Failure and Cardiometabolic Disease, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
  • Cubillos-Ruiz JR; Department of Internal Medicine (Cardiology) and.
  • Alcaide P; Department of Molecular Biology, UT Southwestern Medical Center, Dallas, Texas, USA.
J Clin Invest ; 133(24)2023 Dec 15.
Article en En | MEDLINE | ID: mdl-37874641
Heart failure with preserved ejection fraction (HFpEF) is a widespread syndrome with limited therapeutic options and poorly understood immune pathophysiology. Using a 2-hit preclinical model of cardiometabolic HFpEF that induces obesity and hypertension, we found that cardiac T cell infiltration and lymphoid expansion occurred concomitantly with cardiac pathology and that diastolic dysfunction, cardiomyocyte hypertrophy, and cardiac phospholamban phosphorylation were T cell dependent. Heart-infiltrating T cells were not restricted to cardiac antigens and were uniquely characterized by impaired activation of the inositol-requiring enzyme 1α/X-box-binding protein 1 (IRE1α/XBP1) arm of the unfolded protein response. Notably, selective ablation of XBP1 in T cells enhanced their persistence in the heart and lymphoid organs of mice with preclinical HFpEF. Furthermore, T cell IRE1α/XBP1 activation was restored after withdrawal of the 2 comorbidities inducing HFpEF, resulting in partial improvement of cardiac pathology. Our results demonstrated that diastolic dysfunction and cardiomyocyte hypertrophy in preclinical HFpEF were T cell dependent and that reversible dysregulation of the T cell IRE1α/XBP1 axis was a T cell signature of HFpEF.
Asunto(s)
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Cardíaca / Cardiomiopatías Límite: Animals Idioma: En Revista: J Clin Invest Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Insuficiencia Cardíaca / Cardiomiopatías Límite: Animals Idioma: En Revista: J Clin Invest Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos