Relaxin is a reproductive
hormone that has historically been characterized as being responsible for pubic ligament loosening and cervical ripening. Recently,
relaxin has been associated with neovascularization of the endometrial lining of the uterus, potentially via specific induction of
vascular endothelial growth factor. Previously conducted clinical studies using partially purified porcine
relaxin have described
relaxin's ability to stimulate the healing of ischemic
wounds, suggesting that
relaxin may also have angiogenic effects at sites of ischemic wound healing. In the present study,
relaxin's angiogenic effects in the context of
wound repair were tested in rodent models of angiogenesis and wound healing.
Relaxin showed an ability to stimulate new blood vessel formation, particularly at ischemic
wound sites, and to induce both
vascular endothelial growth factor and
basic fibroblast growth factor specifically in cells, presumably including macrophages, collected from
wound sites. Resident macrophages collected from nonwound sites, such as the lung, did not show altered expression of these
cytokines following
relaxin administration. Because angiogenic
wound cells are frequently macrophages, THP-1 cells, a cell line of monocyte lineage that binds
relaxin specifically, were tested for and shown to induce
vascular endothelial growth factor and
basic fibroblast growth factor in response to
relaxin. In conclusion,
relaxin may be useful in the treatment of ischemic
wounds by stimulating angiogenesis via the induction of
vascular endothelial growth factor and
basic fibroblast growth factor in
wound macrophages.