Language

English

Publication Date

8-5-2026

Journal

Communications Biology

DOI

10.1038/s42003-026-10740-9

PMID

42581147

PMCID

PMC13462327

PubMedCentral® Posted Date

8-5-2026

PubMedCentral® Full Text Version

Post-print

Abstract

Gla proteins are a vitamin K-dependent family long studied for their roles in blood clotting and vascular calcification. This review examines their broader involvement in cardiovascular disease, particularly cardiac fibrosis. We highlight that their functions are context-dependent, varying with disease stage and cellular environment, and that several occur independently of γ-carboxylation, challenging the view that this modification is universally required for their function. By comparing fibrosis across the heart, lung, liver, and kidney, we distinguish shared from organ-specific mechanisms. Finally, we discuss prospective therapies, from vitamin K supplementation to receptor-targeted approaches, and the questions that remain before clinical translation.

Keywords

Humans, Cardiovascular Diseases, Animals, Fibrosis, Matrix Gla Protein, Calcium-Binding Proteins, Extracellular Matrix Proteins, Vitamin K, Myocardium, Mechanisms of disease, Cardiovascular biology, Post-translational modifications

Published Open-Access

yes

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