Abstract
Although peripheral artery disease (PAD) is a major health problem, there have been limited advances in medical therapies. In PAD patients, angiogenesis is regarded as a promising therapeutic strategy to promote new arterial vessels and improve perfusion of ischemic tissue. Autophagy plays a critical role in catabolic processes for cell survival under normal and stressful conditions and plays fundamental biological roles in various cellular functions. In the present study, we showed that autophagy in endothelial cells is important for the repair and regeneration of damaged tissues. In a hindlimb ischemia mouse model, autophagy was stimulated in endothelial cells of the quadriceps muscle, and adjacent cells proliferated and regenerated. The autophagy pathway was induced under prolonged hypoxia in endothelial cells, and autophagy increased angiogenic activities. Moreover, conditioned media from endothelial cells blocked autophagy and inhibited the proliferation of muscle cells, suggesting that autophagic stimulation in endothelial cells affects the survival of adjacent cells, such as muscle. Collectively, hypoxia/ischemia-induced autophagy angiogenesis, and the damaged tissue surrounded by neo-vessels was regenerated in an ischemia model. Therefore, we strongly suggest that stimulation of autophagy in endothelial cells may be a potent therapeutic strategy in severe vascular diseases, including PAD.
Highlights
Peripheral arterial disease (PAD) is a general manifestation of atherosclerosis in which obstruction of arterial flow limits blood supply to both upper and lower extremities, most frequently affecting the lower limbs[1,2]
Discussion angiogenesis is regarded as a promising treatment strategy for patients with peripheral artery disease (PAD) and severe vascular diseases, the use of these strategies in clinical application has not been successful so far[5]
We used an hindlimb ischemia (HLI) mouse model to mimic PAD, which resulted in deep distal ischemia
Summary
Peripheral arterial disease (PAD) is a general manifestation of atherosclerosis in which obstruction of arterial flow limits blood supply to both upper and lower extremities, most frequently affecting the lower limbs[1,2]. In patients with PAD, revascularization is the preferred therapeutic strategy, and the main strategy in therapeutic angiogenesis is to promote the development of new. The hindlimb ischemia (HLI) model involves acute interruption of arterial supply and has generally been used as a preclinical method to assess angiogenic and arteriogenic regulation in PAD6,7. Angiogenesis is regulated by the coordination of a complicated balance of angiogenic growth factors and inhibitors to induce and sustain the endothelial cell migration and proliferation over a limited time period that is required for tissue repair[9].
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