Liver-heart cross-talk mediated by coagulation factor XI protects against heart failure.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 36137043.
- Also identified by DOI 10.1126/science.abn0910 and PMC identifier 9639660.
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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.
Medical subject headings
- Bone Morphogenetic Protein 7
- Factor XI
- Heart Failure
- Liver
- Myocardium