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Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure.
Cao, Yang; Wang, Yuchen; Zhou, Zhenqi; Pan, Calvin; Jiang, Ling; Zhou, Zhiqiang; Meng, Yonghong; Charugundla, Sarada; Li, Tao; Allayee, Hooman; Seldin, Marcus M; Lusis, Aldons J.
Afiliação
  • Cao Y; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Wang Y; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Zhou Z; Division of Endocrinology, Diabetes and Hypertension, Department of Medicine, University of California, Los Angeles, CA 90095, USA.
  • Pan C; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Jiang L; Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.
  • Zhou Z; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Meng Y; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Charugundla S; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
  • Li T; Department of Anesthesiology, Laboratory of Mitochondria and Metabolism, West China Hospital of Sichuan University, Chengdu 610041, China.
  • Allayee H; Departments of Population and Public Health Sciences and Biochemistry and Molecular Medicine, University of Southern California Keck School of Medicine, Los Angeles, CA 90089, USA.
  • Seldin MM; Department of Biological Chemistry and Center for Epigenetics and Metabolism, University of California, Irvine School of Medicine, Irvine, CA 92697, USA.
  • Lusis AJ; Department of Medicine, Division of Cardiology, University of California, Los Angeles, CA 90095, USA.
Science ; 377(6613): 1399-1406, 2022 09 23.
Article em En | MEDLINE | ID: mdl-36137043
ABSTRACT
Tissue-tissue communication by endocrine factors is a vital mechanism for physiologic homeostasis. A systems genetics analysis of transcriptomic and functional data from a cohort of diverse, inbred strains of mice predicted that coagulation factor XI (FXI), a liver-derived protein, protects against diastolic dysfunction, a key trait of heart failure with preserved ejection fraction. This was confirmed using gain- and loss-of-function studies, and FXI was found to activate the bone morphogenetic protein (BMP)-SMAD1/5 pathway in the heart. The proteolytic activity of FXI is required for the cleavage and activation of extracellular matrix-associated BMP7 in the heart, thus inhibiting genes involved in inflammation and fibrosis. Our results reveal a protective role of FXI in heart injury that is distinct from its role in coagulation.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator XI / Proteína Morfogenética Óssea 7 / Insuficiência Cardíaca / Fígado / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Fator XI / Proteína Morfogenética Óssea 7 / Insuficiência Cardíaca / Fígado / Miocárdio Tipo de estudo: Prognostic_studies Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2022 Tipo de documento: Article