Low-Intensity Pulsed Ultrasound Induces Angiogenesis and Ameliorates Left Ventricular Dysfunction in a Porcine Model of Chronic Myocardial Ischemia

Abstract

BackgroundAlthough a significant progress has been made in the management of ischemic heart disease (IHD), the number of severe IHD patients is increasing. Thus, it is crucial to develop new, non-invasive therapeutic strategies. In the present study, we aimed to develop low-intensity pulsed ultrasound (LIPUS) therapy for the treatment of IHD.Methods and ResultsWe first confirmed that in cultured human endothelial cells, LIPUS significantly up-regulated mRNA expression of vascular endothelial growth factor (VEGF) with a peak at 32-cycle (P<0.05). Then, we examined the in vivo effects of LIPUS in a porcine model of chronic myocardial ischemia with reduced left ventricular ejection fraction (LVEF) (n = 28). The heart was treated with either sham (n = 14) or LIPUS (32-cycle with 193 mW/cm2 for 20 min, n = 14) at 3 different short axis levels. Four weeks after the treatment, LVEF was significantly improved in the LIPUS group (46±4 to 57±5%, P<0.05) without any adverse effects, whereas it remained unchanged in the sham group (46±5 to 47±6%, P = 0.33). Capillary density in the ischemic region was significantly increased in the LIPUS group compared with the control group (1084±175 vs. 858±151/mm2, P<0.05). Regional myocardial blood flow was also significantly improved in the LIPUS group (0.78±0.2 to 1.39±0.4 ml/min/g, P<0.05), but not in the control group (0.84±0.3 to 0.97±0.4 ml/min/g). Western blot analysis showed that VEGF, eNOS and bFGF were all significantly up-regulated only in the LIPUS group.ConclusionsThese results suggest that the LIPUS therapy is promising as a new, non-invasive therapy for IHD.

Low-Intensity Pulsed Ultrasound Prevents the Oxidative Stress Induced Endothelial-Mesenchymal Transition in Human Aortic Endothelial Cells

“…Over the past 3 0 years, LIPUS has been used as a principal non-invasive therapy for effective promotion of healing of fractures [15] and regeneration of damaged peripheral nerves [16]. LIPUS has also been tested for its potential application to ameliorating left ventricular remodeling in mice with post-myocardial infarction [17]. However, the studies on the role of LIPUS in endothelial injury have been rather sparse.…”

In vivo repair of rat transected sciatic nerve by low-intensity pulsed ultrasound and induced pluripotent stem cells-derived neural crest stem cells

“…On one hand, iPSCs-NCSCs can differentiate into vascular cells and neurons, which could accelerate the vascular and nerve regeneration during the restore of injured nerve (Kane et al 2011). On the other hand, LIPUS could induce angiogenesis (Hanawa et al 2014) and promote neural differentiation (Lv et al 2013). In addition, LIPUS could speed up the exchanges of nutrients and toxic substances which are good for the formation of nerve filaments (Chen et al 2010).…”

Low-intensity pulsed ultrasound promotes cell motility through vinculin-controlled Rac1 GTPase activity

“…Many in vivo studies have demonstrated that LIPUS can be beneficial in improving healing in several other tissue types, including the skin wounds of diabetic and aged mice by increasing fibroblast migration into the wound site (Roper et al, 2015), ischemic heart disease by increasing angiogenesis (Hanawa et al, 2014), tendon repair (Jeremias Junior et al, 2011;Lu et al, 2016) by increasing collagen synthesis (Fu et al, 2010), and muscle repair after injury by increasing myofibre regeneration .…”