16
The exact mechanism by which C1-INH deficiency causes
angioedema has not been delineated.
5-7
To a large degree,
it results from faulty, uninhibited activation of the KKS.
12,24,27
C1-INH acts at the headwaters of various enzyme cascades,
forming covalent bonds with target proteases and thereby
inhibiting their function.
27,28
The mechanisms of action are described in greater detail in
chapter 7 of this monograph. For now, suffice it to say that
the C1-INH molecule plays an important role as an early
downregulator in at least 4 distinct, yet interconnected,
enzyme cascades (Figure 6):
5,6,29
•
Complement system
•
KKS
•
Fibrinolytic system
•
Coagulation cascade.
Figure 6 – C1-INH Acts as a Downregulator in 4 Enzyme Cascades
Complement System
FXII
FXIIa Initiates
Kallikrein
HMWK=High molecular weight kininogen.
Adapted from 29.
Kallikrein Activates
More FXIIa
Kallikrein
Pre-
Kallikrein
Kallikrein
Bradykinin Receptor
Vascular Permeability
Angioedema
HMWK Cleaved to
Release Bradykinin Bradykinin
FXIIa
HMWK
HMWK
C1-INH
Fibrinolytic System
Coagulation Cascade
Kallikrein-Kinin System
