Effect of Vessel Stiffening and High Pulsatility Flow on Contractile Function and Proliferation of Small Arterial Cells

Recent studies have identified arterial stiffening as a predictor of some vascular diseases such as pulmonary hypertension, which is characterized by dysfunction of small arteries. Stiffening is shown to cause changes in blood flow, extending high pulsatile flow into small arteries that normally experience steady flow conditions (Chui 2004). However, few studies have investigated the mechanisms underlying the effects of arterial stiffening on vascular remodeling. We hypothesized that arterial stiffness effects dysfunction of downstream vascular endothelium and smooth muscle through changes in flow pulsatility. Previously we developed a flow system to study the influence of pulse flow waves, by modulating upstream stiffness, on downstream mimetic vascular cell co-culture. With this system, the present study examines contractile and proliferating protein expressions of smooth muscle cell (SMC) co-cultured with endothelial cell (EC). The endothelium, directly interfaces with the blood flow, and transduces mechanical signals to underlying SMC (Stegemann 2005). We recently showed that high pulsatile flow induced EC dysfunction. Therefore, we further asked whether high pulsatility flow would cause characteristic changes of small arterial SMC in the hypertension condition such as smooth muscle hyperplasia (increased cell proliferation) and hypertrophy (increased contractile proteins) (Voelkel 1997), and whether these changes would be mediated by EC dysfunction.