Component C3
C3 is mainly produced by the liver, monocytes, and macrophages. Several other cells like fibroblasts, epithelial cells, endothelial cells, astrocytes, adipocytes, and myoepithelial cells have all been reported to be potential extrahepatic sources of complement molecules in tissues (Chen et al., 2020a). Evolutionary theory suggests that nature ”preserves” its most vital components by multi-tasking them. This certainly applies to C3. It has been identified in sponges like phylum Porifera (Liszewski et al., 2017). A primitive version of C3 likely comprised the first element of the complements system and functioned intracellular. It can be speculated that the intracellular C3 also engaged in key metabolic processes, some of which are retained in modern times. With the advent of multi-cellularity and the circulatory system, C3 evolved its role as a secreted protein.
Elevated levels of serum C3 are associated with prehypertension in a study with over 7000 individuals and high C3 concentrations in plasma are associated with future increases in blood pressure and the development of hypertension (Bao et al., 2017; Engström et al., 2007). Concerning animal models, the role of C3 has been examined in spontaneously hypertensive rats and DOCA salt hypertension.