In vitro effects of progesterone and the synthetic progestin medroxyprogesterone acetate on vascular remodeling

In this work we tested the hypothesis whether progesterone (Pg) or the synthetic progestin medroxyprogesterone acetate (MPA) could be involved in the regulation of events involved in vascular remodeling. Results revealed an enhancement in the capillary-like tubes formation induced by both progestogens. Unlike MPA, Pg acts through VEGF, nitric oxide, PI3K and ERK1/2 signaling pathways. However, the MPA effect depends on platelet activation. Under stress conditions, the proangiogenic action of Pg and MPA was sustained. The progestogens exhibit the ability to prevent vascular smooth muscle cells (VSMC) osteogenic transdifferentiation. Besides this antiosteogenic action, on bone cells the progestogens induced osteoblast maturation and mineralization. The mechanism of action of both steroids on vascular and bone cells involves the participation of progesterone receptor. The data presented in this work provide evidence that the progestogens reduce osteogenic-like transdifferentiation of VSMC and promote angiogenesis with a slight different mechanism of action elicited by each steroid.