Skeletal muscle MiR-210 expression is associated with mitochondrial function in peripheral artery disease patients.
Skeletal muscle MiR-210 expression is associated with mitochondrial function in peripheral artery disease patients.
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DOI：
10.1016/j.trsl.2022.03.003
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发表时间：
2022-08
期刊：
影响因子：
--
通讯作者：
Koutakis P
中科院分区：
文献类型：
--
作者：
Ismaeel A;Fletcher E;Miserlis D;Wechsler M;Papoutsi E;Haynatzki G;Smith RS;Bohannon WT;Koutakis P
先前的研究表明，外周动脉疾病（PAD）患者的循环microRNA（miR）-210水平升高。已知miR-210是线粒体呼吸的负调节因子;然而，miR-210与线粒体功能之间的关系尚未在PAD中研究。我们旨在比较PAD患者与非PAD对照（CON）的骨骼肌miR-210表达，并检查miR-210表达与线粒体功能之间的关系。通过高分辨率呼吸测定法分析CON（n=20）、间歇性跛行（IC）患者（n=20）和严重肢体缺血（CLI）患者（n=20）的骨骼肌活检，以测量透化纤维的线粒体呼吸。还通过实时PCR分析样品的miR-210表达。与CON相比，IC和CLI肌肉中的miR-210表达显著升高（分别为p=0.008和p<0.001）。IC患者的电子传递链（ETC）复合物II（p=0.001）和IV（p<0.001）的线粒体呼吸显著降低。此外，CLI患者在复合物I（状态2：p=0.04，状态3：p=0.003）、组合I和II（p<0.001）、II（p<0.001）和IV（p<0.001）期间显示呼吸显著减少。PAD肌肉中miR-210靶标、细胞色素c氧化酶组装因子血红素A：法尼基转移酶（COX 10）和铁硫簇组装酶（ISCU）的表达下调。MiR-210可能在细胞对缺氧的适应中起作用，并可能参与与PAD相关的代谢性肌病。
Previous studies have demonstrated that circulating microRNA (miR)-210 levels are elevated in peripheral artery disease (PAD) patients. MiR-210 is known to be a negative regulator of mitochondrial respiration; however, the relationship between miR-210 and mitochondrial function has yet to be studied in PAD. We aimed to compare skeletal muscle miR-210 expression of PAD patients to non-PAD controls (CON) and to examine the relationship between miR-210 expression and mitochondrial function. Skeletal muscle biopsies from CON (n=20), intermittent claudication (IC) patients (n=20), and critical limb ischemia (CLI) patients (n=20) were analyzed by high-resolution respirometry to measure mitochondrial respiration of permeabilized fibers. Samples were also analyzed for miR-210 expression by real-time PCR. MiR-210 expression was significantly elevated in IC and CLI muscle compared to CON (p=0.008 and p<0.001, respectively). Mitochondrial respiration of electron transport chain (ETC) Complexes II (p=0.001) and IV (p<0.001) were significantly reduced in IC patients. Further, CLI patients demonstrated significant reductions in respiration during Complexes I (state 2: p=0.04, state 3: p=0.003), combined I and II (p<0.001), II (p<0.001), and IV (p<0.001). The expression of the miR-210 targets, cytochrome c oxidase assembly factor heme A:farnesyltransferase (COX10) and iron-sulfur cluster assembly enzyme (ISCU) were down-regulated in PAD muscle. MiR-210 may play a role in the cellular adaptation to hypoxia and may be involved in the metabolic myopathy associated with PAD.
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影响因子：
5.3
作者：
Diaz, Francisca;Fukui, Hirokazu;Moraes, Carlos T.
通讯作者：
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影响因子：
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影响因子：
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作者：
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通讯作者：
Wu JC
DOI：
10.1016/j.ejvs.2019.08.011
发表时间：
2020-01-01
影响因子：
5.7
作者：
Gratl, Alexandra;Frese, Jan;Greiner, Andreas
通讯作者：
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