C1q: A novel angiogenic factor?

We have recently shown that endothelial cells (ECs) isolated from human decidua synthesize C1q and express surface-bound C1q under physiological conditions [Bulla et al., 2008. Mol. Immunol.]. Since decidua is a typical site of vascular remodelling and active angiogenic process, we sought to ascertain whether C1q may play a role in promoting angiogenesis using HUVEC in a number of experimental approaches. First, we tested the ability of C1q to induce leakage of FITC-BSA through a monolayer of ECs, as a measure of increased permeability, which is currently considered an initial event of angiogenesis. C1q induced a permeabilizing effect comparable to that of bradykinin, used as a positive control. Next, we found that C1q was able to induce EC proliferation and to act as a chemotactic factor recruiting ECs in a transwell model system. C1q also promoted the motility of ECs in the wound healing assay as evaluated by the ability of these cells to cover the scratched area of an EC monolayer. To further assess whether C1q may stimulate the formation of new vessels, we used an in vitro assay of tube formation, in which ECs are grown in a tridimensional matrix of matrigel to allow the assembly of capillary network. Under these conditions, C1q proved to be as effective as VEGF in inducing tube formation. The pro-angiogenic effect of C1q was also tested in the rat aortic ring assay evaluating the sprouting and branching of new vessels. C1q was found to induce a comparable number of new vessels as VEGF, but with more branches. Taken together, these data disclose an unexpected pro-angiogenic effect of C1q.