Role of albumin in regulating platelet function

Hypoproteinemia, which occurs in diverse clinical conditions, can cause a range of complications such as thrombosis, which is among the most serious and potentially life-threatening. Albumin is a widely utilized clinical therapeutic agent; however, research regarding its regulatory effects on thrombosis remains limited, and existing clinical evidence presents conflicting findings. The precise mechanisms whereby albumin affects platelet thrombus formation require further investigation.

After co-incubating albumin with platelets, various platelet function experiments were carried out. The participation of signaling pathways and protein structures in the mechanism was verified by means of Western blot technology, protein charge neutralization, and over expression of molecules. Validation was also conducted through the construction of animal models.

Albumin significantly inhibited platelet thrombus formation in a murine model of hypoproteinemia without inducing hemorrhagic risk. Platelet aggregation, integrin activation on the membrane surface, and ATP release induced by various agonists were all inhibited. Transmission electron microscopy and fluorescence confocal microscopy revealed that albumin could suppress granule release, alter granule distribution within platelets, and inhibit platelet spreading. Furthermore, albumin was found to reduce the phosphorylation levels of PKC and Akt in the platelet activation signaling pathway. By neutralizing the surface negative charge of albumin and adding cationic surfactants such as quaternary ammonium salts, we confirmed that the surface negative charge of albumin was critical to the inhibition of platelet aggregation and granule release.

Albumin can inhibit platelet activation and thrombus formation through the negatively charged surface residues and by modulating the PKC and Akt signaling pathways.