Crosstalk between the monocytes and coagulation factor VⅡa aggravates the inflammation in patients with CAD

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.