Figure 3.

Potential Zn²⁺-mediated thrombotic routes in obesity and T2DM and targets for therapy. Altered lipid metabolism in obesity and T2DM results in elevated NEFA levels in the blood. NEFA binding at the FA2 site of HSA prevents procoagulant Zn²⁺ ions from binding at site A. The Zn²⁺ unable to bind HSA is redistributed among the cellular and protein components of the homeostatic mechanism, resulting in thrombotic events. This mechanism of thrombosis can be targeted by using lipid- and glucose-lowering drugs, which lower plasma NEFA levels. Therapeutics with chelating properties may also have potential to prevent free Zn²⁺ ions interacting with homeostatic components. FA2 inhibitors could also be developed to restore Zn²⁺ buffering by HSA. Created with BioRender.com (accessed on 13 September 2021).