Endothelial injury induces vascular smooth muscle cell proliferation in highly localized regions of a direct contact co-culture system.
Though previous studies have indicated a relationship between the proliferation of endothelial cells and vascular smooth muscle cells (VSMCs) in co-culture, the results have been contradictory and the signaling mechanism poorly understood. In this transmembrane co-culture study, VSMCs and endothelial cells were grown to confluence on opposite sides of a microporous membrane to mimic the intima/media border of vessels. The endothelial layer was injured, and then cultured for 3 days, resulting in partial re-endothelialization. VSMC proliferation across from the injured/partially recovered endothelial region was significantly higher than across from the de-endothelialized region (a sevenfold increase) and the uninjured region (a threefold increase). ELISA indicated that PDGF, which was undetectable in uninjured co-culture and homotypic controls, increased after injury and the addition of a piperazinyl-quinazoline carboxamide PDGF receptor inhibitor blocked VSMC proliferation across from the injured/partially recovered region. We conclude that co-culture signaling initiated by endothelial cell injury locally stimulates VSMC proliferation and that this signaling could be mediated by PDGF-BB.
Jacot
Jeffrey G
JG
Department of Biomedical Engineering, Boston University, 44 Cummington St, Boston, MA 02215, USA. jacotj@rice.edu
Wong
Joyce Y
JY