Immunol Res. 2026 May 14;74(1):55. doi: 10.1007/s12026-026-09784-0.
ABSTRACT
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.
PMID:42128959 | DOI:10.1007/s12026-026-09784-0