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).