Table 2.
Overview of molecular crosstalk identified in the topmost implicated plasma proteins of the coagulation and complement pathways.
| Coagulation | Complement | Effect on Complement | Effect on Coagulation | Reference |
|---|---|---|---|---|
| FXII (↑) | C1Q, C1R (↑) | FXII activates C1 complex |
C1Q inhibits activation of FXII in vitro Platelet activation |
[157–159] |
| FII, FIX, FXI (↑) | C3 (↑) | FIIa, FIXa, and FXIa cleave C3→C3a and C5→C5a |
C3a and C5a increase platelet activation C5a increases tissue factor activity C5a increases expression of PAI-1 on mast cells |
[160–163] |
| FX (↓) | C3, C5 (↑) | FXa cleaves C3 into C3a and C5 into C5a | [160] | |
| PLG (↑) | C5 (↑) | PLN cleaves C5 into C5a | [141] | |
| PLG (↑) | C4BP (↓) |
C4BP binds PLG and increases activation of plasminogen (PLG) to plasmin (PLN) C4BP binds PROS resulting decreased cofactor function of protein S for activated protein C |
[164, 165] | |
| FXI, FXII (↑) | SERPING1 | SERPING1 inhibits FXIa and FXIIa | [166] | |
| SERPING1 | C1R (↑) | SERPING1 inhibits C1R | [167] | |
| A2M (↓) | Thrombin, FXa, PLG (↑) | A2M, C3, and C4 are structurally similar and evolutionarily related | A2M is a protease inhibitor of thrombin, FXa, plasmin | [168–170] |
| Platelets | C7, C8, C9 | C5b6789 (C5b-9) forms the lytic membrane-attack complex |
C5b6789 (C5b-9) affects: Platelet activation; Increased binding of coagulation factors Va and Xa; Increased release of factor V from platelet alpha-granules; Induces endothelial cells to secrete von Willebrand factor; C7 binding interaction with PLG enhances tPA-mediated PLG activation |
[164, 171–173] |
| vWF, TM | CFH (↑) |
CFH and VWF binding interaction enhances CFH cofactor activity and VWF-mediated platelet aggregation CFH and TM binding interaction enhances CFH cofactor activity |
[174–176] | |
| CLU (↑) | CLU binds to C5b-7 and inhibits generation of C5b-9 | [177] | ||
| Thrombin–antithrombin | VTN (↑) | VNT binds to C5b-7 and inhibits C9 polymerization | VTN binds to the thrombin–antithrombin complex (TAT) | [178–180] |
| Protein S | C4BP | C4BP interaction with protein S has no effect on the inhibition of complement activation | C4BP can bind anticoagulant protein S, resulting in a decreased cofactor function of protein S for activated protein C | [181] |
Fold change direction shown for upregulation (↑) and downregulation (↓) is indicated for each protein—shown with corresponding gene name. Proteins identified are shown in bold.