Complement component C1q initiates extrinsic coagulation via the receptor for the globular head of C1q in adventitial fibroblasts and vascular smooth muscle cells

Abstract

Background Vascular diseases are highly associated with inflammation and thrombosis. Elucidating links between these two processes may provide a clearer understanding of these diseases, allowing for the design of more effective treatments. The activation of complement component 1 (C1) is a crucial contributor to innate immunity and is associated with significant concentrations of circulating C1q. Many pathological pathways initiate when C1q interacts with gC1qR. This interaction plays a major role in inflammation observed during atherosclerosis and the initiation of intrinsic coagulation. However, the effects of C1 and the role of C1q/gC1qR on extrinsic coagulation, which is the more physiologically relevant coagulation arm, has not been studied. We hypothesized that C1q binding to gC1qR enhances the expression of tissue factor (TF) in adventitial fibroblasts and vascular smooth muscle cells, the primary TF bearing cells in the body. Methods Using an enzyme‐linked immunosorbent assay approach, TF expression and the role of gC1qR was observed. Cells were conditioned for 1 h with C1q or a gC1qR blocker and C1q, to assess the role of gC1qR. Additionally, cell growth characteristics were monitored to assess changes in viability and metabolic activity. Results Our results indicate that the expression of TF increased significantly after incubation with C1q as compared with unconditioned cells. Cells conditioned with gC1qR blockers and C1q exhibited no change in TF expression when compared with cells conditioned with the blocking antibodies alone. Our results show no significant differences in metabolic activity or cell viability under these conditions. Conclusions This indicates that gC1qR association with C1q induces TF expression and may initiate extrinsic coagulation. Overall, this data illustrates a role for C1q in the activation of extrinsic coagulation and that gC1qR activity may link inflammation and thrombosis.

Diagnostic and Prognostic Value of C1q in Sepsis-Induced Coagulopathy

“… 22 , 23 C1q contributes to coagulation by inhibiting platelet adhesion, IgG adsorption, and reducing the diffusion of adherent platelets. 24 Moreover, research indicates that C1q can directly influence blood coagulation. Bleeding experiments involving C1q-deficient mice and wild-type mice revealed that mice lacking C1q exhibited prolonged bleeding times and increased blood loss, underscoring the direct involvement of C1q in thrombosis during the coagulation process.…”

Complement-Coagulation Cross-talk: Factor H-mediated regulation of the Complement Classical Pathway activation by fibrin clots

“…The interaction of C1q with platelet surface receptors not only enhances platelet procoagulant activity through the expression of integrins and P-selectin but also promotes platelet adhesion to activated endothelial cells ( 74 – 76 ). The role of C1q in modulating the expression of TF in adventitial fibroblasts and coronary artery vascular smooth muscle cells via its binding to gC1qR further implicates it in thrombus formation and hemostasis regulation ( 77 ). Experimental findings, such as the prolonged bleeding and increased blood loss in C1q-deficient mice compared with wild-type animals, underline the direct involvement of C1q in coagulation processes, although the underlying mechanisms warrant further investigation ( 78 , 79 ).…”