A new study reveals that a gut-derived metabolite called trimethylamine N-oxide (TMAO) binds to fibrinogen, a key blood-clotting protein, enhancing clot stability. This finding provides a molecular explanation for how gut-derived compounds may elevate the risk of atherosclerosis, a condition that underpins many heart attacks and strokes.
Researchers from Singh et al. mapped the interaction between TMAO and fibrinogen, identifying specific binding sites and structural changes that increase clot stability. TMAO binds to the β1 calcium-binding site on fibrinogen, altering its structural dynamics and increasing its propensity to form fibrin clots. Clots formed in the presence of TMAO were more resistant to degradation, indicating enhanced stability.
The study also found that TMAO shifts the equilibrium of fibrinogen's β-nodules toward a high-affinity state, facilitating protofibril assembly and accelerating clot formation. These insights could inform future strategies to mitigate cardiovascular risk, such as dietary adjustments or pharmacological interventions.