Critical Limb Ischemia Induces Remodeling of Skeletal Muscle Motor Unit and Myonuclear- and Mitochondrial-Domains
Author:
Mohiuddin Mahir,Lee Nan Hee,Moon June Young,Han Woojin M.,Anderson Shannon E.,Choi Jeongmoon J.,Nakhai Shadi,Tran Thu,Aliya Berna,Kim Do Young,Gerold Aimee,Hansen Laura,Taylor W. Robert,Jang Young C.
Abstract
AbstractCritical limb ischemia, the most severe form of peripheral artery disease, leads to extensive damage and alterations in skeletal muscle homeostasis. Although recent developments towards revascularization therapies have been introduced, there has been limited research into treatments for ischemic myopathy. To elucidate the regenerative mechanism of the muscle stem cell and its niche components in response to ischemic insults, we explored interactions between the vasculature, motor neuron, muscle fiber, and the muscle stem cell. We first investigated changes in the neuromuscular junction and motor neuron innervation following a surgical hindlimb ischemia model of critical limb ischemia in mice. Along with previous findings that support remodeling of the neuromuscular junction, we report that ischemic injury also causes significant alterations to the myofiber through a muscle stem cell-mediated increase of myonuclei number per fiber, a concomitant decrease in myonuclear domain size, and an increase in relative mitochondrial content per myonucleus. These results indicate that as a regenerative response to critical limb ischemia, myofibers exhibit myonuclear expansion to allow enhanced transcriptional support and an increase in mitochondrial content for bioenergetic need of the energy-demanding tissue regeneration.
Publisher
Cold Spring Harbor Laboratory
Reference58 articles.
1. Lower extremity amputation in peripheral artery disease: improving patient outcomes;Vasc Health Risk Manag,2014
2. Role of integrins in angiogenesis;European Journal of Cancer,1996
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献