Peripheral artery disease, caused by chronic arterial occlusion of the lower extremities, affects over 200 million people worldwide. Peripheral artery disease can progress into critical limb ischemia (CLI), its more severe manifestation, which is associated with higher risk of limb amputation and cardiovascular death. Aiming to improve tissue perfusion, therapeutic angiogenesis held promise to improve ischemic limbs using delivery of growth factors but has not successfully translated into benefits for patients. Moreover, accumulating studies suggest that impaired downstream signaling of these growth factors (or angiogenic resistance) may significantly contribute to CLI, particularly under harsh environments, such as diabetes mellitus. Noncoding RNAs are essential regulators of gene expression that control a range of pathophysiologies relevant to CLI, including angiogenesis/arteriogenesis, hypoxia, inflammation, stem/progenitor cells, and diabetes mellitus. In this review, we summarize the role of noncoding RNAs, including microRNAs and long noncoding RNAs, as functional mediators or biomarkers in the pathophysiology of CLI. A better understanding of these ncRNAs in CLI may provide opportunities for new targets in the prevention, diagnosis, and therapeutic management of this disabling disease state.

中文翻译：

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临界肢体缺血中的非编码RNA。

下肢慢性动脉阻塞引起的周围动脉疾病，影响全球2亿多人。周围动脉疾病可进展为严重肢体缺血（CLI），其表现更为严重，这与肢体截肢和心血管死亡的较高风险相关。为了改善组织灌注，治疗性血管生成有望通过使用生长因子的输送来改善缺血性肢体，但尚未成功地为患者带来益处。此外，越来越多的研究表明，这些生长因子的下游信号传导减弱（或血管生成抗性）可能会显着影响CLI，特别是在恶劣环境下，例如糖尿病。非编码RNA是控制与CLI相关的一系列病理生理的基因表达的重要调节因子，包括血管生成/动脉生成，缺氧，炎症，干/祖细胞和糖尿病。在这篇综述中，我们总结了非编码RNA（包括微RNA和长非编码RNA）在CLI病理生理中作为功能性介体或生物标志物的作用。对CLI中这些ncRNA的更好理解可能会为预防，诊断和治疗这种致残性疾病状态的新靶标提供机会。