Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.

Gla proteins influence cardiovascular disease and fibrosis through context-dependent mechanisms, with some functions independent of gamma-carboxylation, across multiple organs.

• Why it matters: Understanding the diverse roles of Gla proteins in fibrosis is crucial because it can reveal new therapeutic targets for cardiovascular and organ-specific diseases, addressing gaps in current knowledge about their functions.
• What they did: The review compares fibrosis mechanisms in the heart, lung, liver, and kidney, highlighting the variability in Gla protein functions and discussing potential therapies such as vitamin K supplementation and receptor-targeted strategies.
• The result: This work clarifies shared and organ-specific fibrosis pathways involving Gla proteins, paving the way for targeted treatments and raising important questions for future clinical translation.