Meteorin-like/Meteorin-β protects heart against cardiac dysfunction

Autor: Glòria Garrabou, Gemma Ferrer-Curriu, Francesc Villarroya, Anna Planavila, Mariona Guitart-Mampel, Celia Rupérez, Monica Zamora, Josep Lupón, Laura Florit, Fatima Crispi, Aina Cervera-Barea, Joaquim Fernández-Solà, Antoni Bayes-Genis
Rok vydání: 2021
Předmět:
Male
0301 basic medicine
medicine.medical_specialty
Cardiotonic Agents
Immunology
Adipose tissue
Blood Pressure
Cardiomegaly
030204 cardiovascular system & hematology
Carbohydrate metabolism
Article
Protein metabolism
03 medical and health sciences
0302 clinical medicine
Fibrosis
Internal medicine
Cardiovascular Biology
medicine
Animals
Humans
Immunology and Allergy
Endocrine system
Myocytes
Cardiac
PPAR alpha
Nerve Growth Factors
Muscle
Skeletal
Autocrine signalling
Cells
Cultured
Heart Failure
Mice
Knockout
Malalties cardiovasculars
business.industry
Skeletal muscle
medicine.disease
Mice
Inbred C57BL
Disease Models
Animal
Cardiovascular diseases
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Animals
Newborn
Gene Expression Regulation
Echocardiography
Heart failure
cardiovascular system
Biomarker (medicine)
Metabolisme de proteïnes
business
Zdroj: The Journal of Experimental Medicine
Dipòsit Digital de la UB
Universidad de Barcelona
ISSN: 1540-9538
0022-1007
DOI: 10.1084/jem.20201206
Popis: Rupérez et al. report the discovery of the protein Metrnβ as a new cardiokine with cardioprotective actions. They established that the heart produces Metrnβ, which in turn protects against cardiac hypertrophy. Metrnβ is also a new prognostic biomarker in heart failure patients.
Meteorin-like/Meteorin-β (Metrnl/Metrnβ) is a secreted protein produced by skeletal muscle and adipose tissue that exerts metabolic actions that improve glucose metabolism. The role of Metrnβ in cardiac disease is completely unknown. Here, we show that Metrnβ-null mice exhibit asymmetrical cardiac hypertrophy, fibrosis, and enhanced signs of cardiac dysfunction in response to isoproterenol-induced cardiac hypertrophy and aging. Conversely, adeno-associated virus–mediated specific overexpression of Metrnβ in the heart prevents the development of cardiac remodeling. Furthermore, Metrnβ inhibits cardiac hypertrophy development in cardiomyocytes in vitro, indicating a direct effect on cardiac cells. Antibody-mediated blockage of Metrnβ in cardiomyocyte cell cultures indicated an autocrine action of Metrnβ on the heart, in addition to an endocrine action. Moreover, Metrnβ is highly produced in the heart, and analysis of circulating Metrnβ concentrations in a large cohort of patients reveals that it is a new biomarker of heart failure with an independent prognostic value.
Graphical Abstract
Databáze: OpenAIRE
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