Stimulation of angiogenesis using single-pulse low-pressure shock wave treatment.

Abstract

Endothelial cells respond to mechanical stimuli such as stretch. This property can be exploited with caution to induce angiogenesis which will have immense potential to treat pathological conditions associated with insufficient angiogenesis. The primary aim of this study is to test if low-pressure shock waves can be used to induce angiogenesis. Using a simple diaphragm-based shock tube, we demonstrate that a single pulse of low pressure (0.4bar) shock wave is enough to induce proliferation in bovine aortic endothelial cells and human pulmonary microvascular endothelial cells. We show that this is associated with enhanced Ca++ influx and phosphorylation of phosphatidylinositol-3-kinase (PI3K) which is normally observed when endothelial cells are exposed to stretch. We also demonstrate the pro-angiogenic effect of shock waves of single pulse (per dose) using murine back punch wound model. Shock wave treated mice showed enhanced wound-induced angiogenesis as reflected by increased vascular area and vessel length. They also showed accelerated wound closure compared to control mice. Overall, our study shows that just a single pulse/shot (per dose) of shock waves can be used to induce angiogenesis. Importantly, we demonstrate this effect using a pulse of low-pressure shock waves (0.4bar, in vitro and 0.15bar, in vivo). KEY MESSAGES: Low-pressure single-pulse shock waves can induce endothelial cell migration and proliferation. This effect is endothelial cell specific. These shock waves enhance wound-induced angiogenesis in vivo. These shock waves can also accelerate wound healing in vivo.