C3 in the DOCA salt hypertension model
An increased expression of likely harmful C3 is also observed in another mouse-based hypertension model. The perivascular adipose tissue in the DOCA salt treated mice displays a clear increase in C3 expression (Ruan et al., 2015). Bone marrow transplantation from C3 knockout mice into wild type mice lowered vascular injury in DOCA salt exposed mice. This was accompanied by a greatly reduced deposition of C5a in the perivascular adipose tissue after transplantation of C3 deficient bone marrow. In addition, treatment with a C5aR peptide agonist aggravated vascular hypertrophy and fibrosis in DOCA salt treated mice. No effect on blood pressure was found (Ruan & Gao, 2019). These findings suggest that C3 from bone marrow derived cells contribute to the DOCA salt hypertensive vascular remodeling process largely via the downstream generation of C5a, most likely via C3/C5 convertase formation.