<p>The underlying proinflammatory mechanism of coagulation factor VⅡ in coronary artery disease (CAD) remains unclear. According to the inclusion criteria, 24 non-CAD subjects and 24 patients with CAD were enrolled. The expression levels of pro-inflammatory (CD14⁺CD86⁺, CD14⁺CD163^-), anti-inflammatory monocytes (CD14⁺CD163⁺), CD14⁺CD142⁺ and CD14⁺PAR2⁺ monocytes in peripheral blood were detected by flow cytometry. The levels of TNF-α, IL-1β, IL-6, IL-10, and FVⅡ in plasma were determined by ELISA. In vitro experiments were conducted to induce inflammatory THP-1 by FVⅡa. The FVⅡa/TF complex inhibitor PCI-27,483 and PAR2 antagonist AZ3451 were used to clarify the mechanisms. Compared with the control group, the percentage of CD14⁺CD86⁺ pro-inflammatory monocytes were significantly increased in the CAD group, and further elevated after PCI. The results of the levels of CD14⁺CD142⁺ and CD14⁺PAR2⁺ monocytes showed the same trends with CD14⁺CD86⁺ pro-inflammatory monocytes. The levels of CD14⁺CD163⁺ anti-inflammatory monocytes and IL-10 were decreased in CAD patients, but increased after PCI. The pro-inflammatory factors and FVⅡ were significantly elevated in the CAD group and significantly decreased after PCI. Correlation analysis revealed that FVⅡ, TF, and PAR2 were significantly associated with CD14⁺CD86⁺ pro-inflammatory monocytes, and inflammatory factors. In vitro studies further confirmed that the FVⅡa/TF coagulation complex and PAR2 could activate NF-κB in monocytes and aggravate inflammation. Our findings suggest that crosstalk between monocytes and the coagulation complex might contribute to residual inflammation in CAD, potentially involving the FVIIa/TF/PAR2-NF-κB signaling pathway. Based on these observations, we hypothesize that blocking the interaction between clotting factors and monocytes could represent a promising therapeutic strategy to mitigate residual inflammation, but further rigorous experiments are needed for verification.</p> Graphical abstract <p></p>