Abstract 535: Shear Stress Upregulates Placental Growth Factor in an in vitro Model of the Vessel Wall in a Reactive Oxygen Species Dependent Manner

Arteriogenesis is the process by which mature arteries form from collateral arterioles after upstream arterial stenosis or occlusion. During collateral remodeling, monocytes are recruited to the vessel wall. Placental growth factor (PLGF) is a potent stimulator of arteriogenesis via monocyte recruitment. Although fluid shear stress is thought to be the primary signal for arteriogenesis, its role in regulating PLGF expression is unknown. However, PLGF is increased in collaterals by upstream arterial ligation. Therefore, we hypothesized that PLGF expression is regulated by shear stress. To test this hypothesis, we created an in vitro model of coronary vessels, consisting of human coronary artery endothelial cells (HCAEC) and human coronary artery smooth muscle cells (HCASMC) cocultured on porous Transwell inserts. HCAEC were then exposed to normal (low) shear stress (LSS) (time average 0.7 dyne/cm2), high shear stress (HSS) (time average 12.4 dyne/cm2), or no shear (static) for 2 hours. HSS significantly increased secreted PLGF protein compared to LSS (~25%, n= 5, p < 0.05) as determined by ELISA. Knockdown of PLGF by siRNA in HCAEC significantly reduced secreted PLGF protein while knockdown in HCASMC had no significant effect, suggesting HCAEC are the primary source of PLGF protein (n=4, p