CTRP3 is also demonstrated to play a large role in angiogenesis and endothelial cell proliferation (2, 23, 45, 81). For example, during the recovery period following rat carotid artery balloon-injury model CTRP3 expression increases dramatically (35). Interestingly CTRP3 may not act directly on the endothelial cells, but through indirect pathways mediated by cardiac or smooth muscles cells. Direct treatment of Human Umbilical Vein Endothelial Cells (HUVEC) with CTRP3 had no direct effect on capillary-like structures formation (tube formation), Akt phosphorylation or hypoxiainducible factor 1, alpha subunit (HIF1α) orVascular endothelial growth factor (VEGF) expression (81). However, conditioned media from primary cardiomyocytes treated with CTRP3 induced HUVEC tube formation, indicating the presence of CTRP3-induced cardiomyocyte-secreted paracrine factors (81). However, the direct effect of CTRP3 on HUVEC cells cannot be completely ruled out as Yi et al. (2012) (81) used bacterial expressed CTRP3 directly on HUVEC cells and used mammalian expressed CTRP3 in vivo. This discrepancy may indicate a post-translational modification is required for the CTRP3-induced effects on vascular endothelium.
