Progesterone Inhibits Vascular Endothelial Cell Migration, Invasion, Monocyte Adhesion, and Focal Adhesion Signaling Through Membrane Progesterone Receptor Alpha (mprα, PAQR7) and Nuclear Progesterone Receptor (Npr)

Whereas progesterone has been shown to cause vascular smooth muscle cell relaxation, other beneficial vascular effects of progesterone, including preventing the onset of atherosclerosis, remain unclear. The results show that 16 hours treatments with specific agonists for membrane progesterone receptors (mPRs), OD 02-0, and nuclear PRs (nPRs), R5020, inhibited pre-atherosclerotic events in human umbilical vein endothelial cells (HUVECs), decreasing focal adhesion by monocytes, HUVEC migration and invasion, along with vinculin expression. Progesterone and OD 02-0, but not R5020, inhibited phosphorylation of Src and FAK, two critical kinases of focal adhesion signaling, within 20 minutes. However, after 16 hours OD 02-0 was no longer effective, while both progesterone and R5020 decreased activity of the two kinases. Knockdown of receptor expression with siRNA confirmed that mPRα mediates short-term and nPR long-term inhibitory effects of progesterone on focal adhesion signaling. Thus, progesterone inhibition of FAK signaling and pre-atherosclerosis is coordinated through mPRα and nPRs.