Complement C5
Raij et al . treated C5 deficient mice and C5 sufficient mice that differ in the single gene locus responsible for the presence or absence of the complement C5 component with DOCA salt. C5 deficient mice can neither generate C5a nor form the C5b-9 complex. Hypertensive C5 deficient mice developed more glomerular capillary loop dilatation and larger glomerular capillary tuft volumes than C5 sufficient mice. However, DOCA C5 sufficient mice, compared to DOCA C5 deficient mice, had significantly more glomerular cell proliferation, cell necrosis, extra capillary proliferation and proteinuria. After 16 weeks, C5 sufficient mice, in comparison to C5 deficient mice, had more severe glomerulosclerosis, proteinuria and renal insufficiency. These changes occurred despite levels of hypertension that were similar in C5 sufficient and C5 deficient mice throughout the whole study period (Raij et al., 1989). These data suggest that C5 and/or C5b-9 play an important role in hypertensive glomerular injury but that these roles are complex and need to be carefully defined during the different stages of the disease.
This latter notion is also supported by the finding that mice lacking CD59a have elevated deposition of membrane attack complex. CD59 is the primary regulator of the membrane attack complex formation. However, and somewhat surprisingly, no increased blood pressure or cardiovascular injury was found in response to angiotensin II infusion (Coles et al., 2007).