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

Abstract

In this work we tested the hypothesis whether progesterone (Pg)or the synthetic progestin medroxyprogesterone acetate (MPA) could beinvolved in the regulation of events involved in vascular remodeling.Results revealed an enhancement in the capillary-like tubes formationinduced by both progestogens. Unlike MPA, Pg acts through VEGF, nitricoxide, PI3K and ERK1/2 signaling pathways. However, the MPA effectdepends on platelet activation. Under stress conditions, theproangiogenic action of Pg and MPA was sustained. The progestogensexhibit the ability to prevent vascular smooth muscle cells (VSMC)osteogenic transdifferentiation. Besides this antiosteogenic action, onbone cells the progestogens induced osteoblast maturation andmineralization. The mechanism of action of both steroids on vascular andbone cells involves the participation of progesterone receptor. The datapresented in this work provide evidence that the progestogens reduceosteogenic-like transdifferentiation of VSMC and promote angiogenesiswith a slight different mechanism of action elicited by each steroid.