Figure 4
Figures 4 summarizes the present knowledge on the role of complement in hypertension and hypertensive end organ damage. Shown is the complement cascade with the three pathways. In the classical pathway, C1q activates smooth muscle cell proliferation by the β catenin pathway. C3 knockout lowers blood pressure in spontaneously hypertensive rats but not mice with angiotensin II infusion. Renin has C3 convertase activity and can convert C3 independent of the three complement pathways. This effect can be inhibited by the renin inhibitor aliskiren. C5 probably by formation of C5b-9 aggravates glomerular sclerosis in DOCA salt hypertensive mice. C5 induces cardiac remodeling in angiotensin II infused since inhibition of C5 by an antibody is protective. Protectin (CD59) inhibits C5b-9. However, knockout of protectin has no effect on blood pressure. Treatment with soluble CR1 has no effect on blood pressure in Dahl salt sensitive rats. C3aR has protective effects in hypertension since knockout of the receptor seems to aggravate injury. The role of C5aR1 seems to be more complex. The C5a-C5aR1 axis aggravates cardiac injury since C5aR1 knockout as well as treatment with the C5aR1 antagonist PMX53 are cardio protective in hypertensive mice and rats. However, also cardio protective effects have been shown in an accelerated model of hypertension. The C5a/C5aR1 axis induces kidney injury. Treatment with a C5a agonistic peptide aggravates vascular remodeling in hypertension. Double knockout of C3aR and C5aR1 lowers blood pressure most likely by an increase of regulatory T cells. No data are available on the role of C5aR2 in hypertension or the effect of complement in hypertensive brain injury. Whether complement plays a role in the development of malignant nephrosclerosis is unclear.