Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration.
Exercise and Ischemia-Activated Pathways in Limb Muscle Angiogenesis and Vascular Regeneration.
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DOI：
10.14797/mdcvj.1304
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发表时间：
2023
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运动对心血管疾病有深远的影响，特别是通过血管重塑和再生。外周动脉疾病（PAD）是一种这样的心血管疾病，从定期锻炼或康复物理治疗中受益，可以减缓疾病进展和延迟截肢。使用PAD和运动模型的各种啮齿动物临床前研究揭示了血管再生的分子途径。在这里，我回顾了骨骼肌中驱动旁分泌再生血管生成的关键运动激活信号通路（核受体，激酶和缺氧诱导因子）。强调骨骼肌的理由是，它是运动过程中招募的最大器官。在运动期间，骨骼肌释放几种肌因子，包括血管生成因子和细胞因子，其通过激活内皮细胞以及通过募集免疫和内皮祖细胞来驱动组织血管再生。这些核心运动激活途径中的一些可以外推到其他器官的血管再生。我还强调了运动研究的未来领域（包括代谢组学，单细胞转录组学和细胞外囊泡生物学），以促进我们对运动如何在分子水平上诱导血管再生的理解，并提出了“运动模拟”治疗血管恢复的想法。
Exercise has a profound effect on cardiovascular disease, particularly through vascular remodeling and regeneration. Peripheral artery disease (PAD) is one such cardiovascular condition that benefits from regular exercise or rehabilitative physical therapy in terms of slowing the progression of disease and delaying amputations. Various rodent pre-clinical studies using models of PAD and exercise have shed light on molecular pathways of vascular regeneration. Here, I review key exercise-activated signaling pathways (nuclear receptors, kinases, and hypoxia inducible factors) in the skeletal muscle that drive paracrine regenerative angiogenesis. The rationale for highlighting the skeletal muscle is that it is the largest organ recruited during exercise. During exercise, skeletal muscle releases several myokines, including angiogenic factors and cytokines that drive tissue vascular regeneration via activation of endothelial cells, as well as by recruiting immune and endothelial progenitor cells. Some of these core exercise-activated pathways can be extrapolated to vascular regeneration in other organs. I also highlight future areas of exercise research (including metabolomics, single cell transcriptomics, and extracellular vesicle biology) to advance our understanding of how exercise induces vascular regeneration at the molecular level, and propose the idea of “exercise-mimicking” therapeutics for vascular recovery.