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Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.
Gergely, Tamás G; Drobni, Zsófia D; Kallikourdis, Marinos; Zhu, Han; Meijers, Wouter C; Neilan, Tomas G; Rassaf, Tienush; Ferdinandy, Péter; Varga, Zoltán V.
Afiliación
  • Gergely TG; Department of Pharmacology and Pharmacotherapy, Semmelweis University, Budapest, Hungary.
  • Drobni ZD; HCEMM-SU Cardiometabolic Immunology Research Group, Budapest, Hungary.
  • Kallikourdis M; MTA-SE Momentum Cardio-Oncology and Cardioimmunology Research Group, Budapest, Hungary.
  • Zhu H; Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
  • Meijers WC; Division of Cardiology, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA.
  • Neilan TG; Department of Biomedical Sciences, Humanitas University, Milan, Italy.
  • Rassaf T; Adaptive Immunity Lab, Humanitas Research Hospital IRCCS, Milan, Italy.
  • Ferdinandy P; Division of Cardiovascular Medicine, Stanford University School of Medicine, Palo Alto, CA, USA.
  • Varga ZV; Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, The Netherlands.
Nat Rev Cardiol ; 21(7): 443-462, 2024 07.
Article en En | MEDLINE | ID: mdl-38279046
ABSTRACT
Immune checkpoint molecules are physiological regulators of the adaptive immune response. Immune checkpoint inhibitors (ICIs), such as monoclonal antibodies targeting programmed cell death protein 1 or cytotoxic T lymphocyte-associated protein 4, have revolutionized cancer treatment and their clinical use is increasing. However, ICIs can cause various immune-related adverse events, including acute and chronic cardiotoxicity. Of these cardiovascular complications, ICI-induced acute fulminant myocarditis is the most studied, although emerging clinical and preclinical data are uncovering the importance of other ICI-related chronic cardiovascular complications, such as accelerated atherosclerosis and non-myocarditis-related heart failure. These complications could be more difficult to diagnose, given that they might only be present alongside other comorbidities. The occurrence of these complications suggests a potential role of immune checkpoint molecules in maintaining cardiovascular homeostasis, and disruption of physiological immune checkpoint signalling might thus lead to cardiac pathologies, including heart failure. Although inflammation is a long-known contributor to the development of heart failure, the therapeutic targeting of pro-inflammatory pathways has not been successful thus far. The increasingly recognized role of immune checkpoint molecules in the failing heart highlights their potential use as immunotherapeutic targets for heart failure. In this Review, we summarize the available data on ICI-induced cardiac dysfunction and heart failure, and discuss how immune checkpoint signalling is altered in the failing heart. Furthermore, we describe how pharmacological targeting of immune checkpoints could be used to treat heart failure.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Puntos de Control Inmunológico / Insuficiencia Cardíaca Límite: Animals / Humans Idioma: En Revista: Nat Rev Cardiol Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores de Puntos de Control Inmunológico / Insuficiencia Cardíaca Límite: Animals / Humans Idioma: En Revista: Nat Rev Cardiol Asunto de la revista: CARDIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Reino Unido