Plasminogen activator inhibitor‐1 can regulate myoendothelial junction formation

Abstract

Myoendothelial junctions are cellular projections that form between the vascular smooth muscle cell and endothelial cell layers of the resistance vasculature by disruption of the internal elastic lamina. How and why these structures form is unknown, but given the location of the MEJ, it is likely that degradation of the internal elastic lamina is required. We have recently identified plasminogen activator inhibitor ‐1 (PAI‐1), a mediator of the fibrinolytic system, as being preferentially localized at the MEJ both in vivo and in vitro (see abstract by Heberlein, et al.). Using Metamorph software analysis on a vascular cell co‐culture model (Isakson et al., 2005), we show that inhibition of PAI‐1 activity using a monoclonal antibody (1000 ng/mL) has an approximate 20% increase in the number of MEJs formed, as identified by phalloidin labeling of actin. Conversely the addition of PAI‐1 (100 ng/mL) results in an approximate 20% decrease in number of MEJs formed. The formation of MEJs in response to PAI‐1 and PAI‐1 monoclonal antibodies appears to be dose‐dependent. These results were compared to MEJ formation in PAI‐1‐/‐ mice. Based on these data we conclude that PAI‐1 may regulate the formation of MEJs in the vasculature. Supported by NIH RO1 088554 and an AHA SDG.