Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation

Regeneration of Mitochondrial Function in Gastrocnemius Muscle in Peripheral Arterial Disease After Successful Revascularisation
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DOI:
10.1016/j.ejvs.2019.08.011
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发表时间:
2020-01-01
影响因子:
5.7
通讯作者:
Greiner, Andreas
Greiner, Andreas
中科院分区:
医学1区
文献类型:
--
作者:
Gratl, Alexandra;Frese, Jan;Greiner, Andreas

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目的:肌病,其特点是改变线粒体功能,是外周动脉疾病的病理生理学的一个中心部分,本研究的目的是调查的影响revascularisation对线粒体function.Methods:高分辨率呼吸测定法被用来调查线粒体呼吸和结果进行归一化柠檬酸合酶活性(CSA),线粒体含量的标志物。入选了10例有症状的外周动脉疾病患者(研究组)和10例无缺血的受试者(对照组)。在血管介入治疗前后进行踝臂指数和超声成像,以确认技术上成功的血运重建。在研究组中,在血管介入治疗前和血运重建后6周从腓肠肌进行肌肉活检。在对照组内,组织收获once.Results:有关于人体测量数据没有显着的组间差异。成功血运重建后,CSA显著增加(术前CSA为281.4(252.4-391.8)nmol/min/mg蛋白质,术后CSA为438.5(361.4-471.3)nmol/min/mg蛋白质; p = 0.01),术后数值恢复至对照受试者的范围(CSA对照组396.6(308.2-435.9))。与术前值相比,线粒体呼吸在氧化磷酸化(P)和电子传递(E)能力方面标准化为CSA,术后显著降低(P术前0.218(0.196-0.266)pmol/(secxmg)(根据CSA)vs.术后0.132根据CSA,(0.116-0.150)pmol/(secxmg),p = 0.007; E术前0.230根据CSA的(0.195-0.279)pmol/(secxmg)与术后0.129(0.120-0.154)pmol/(secxmg),根据CSA,p = .005),意味着术后数值恢复到对照受试者的范围内(P对照组0.124(0.080-0.155)pmol/(secxmg)per CSA; E对照组0.121(0.079-0.125)pmol/(secxmg)per CSA)。结论:这些结果表明,最初受损的线粒体功能和含量在血管重建后可以恢复正常。
Objective: Myopathy, characterised by altered mitochondrial function, is a central part of the pathophysiology of peripheral arterial disease and the aim of this study was to investigate the effect of revascularisation on mitochondrial function.Methods: High resolution respirometry was used to investigate mitochondrial respiration and the results were normalised to citrate synthase activity (CSA), a marker of mitochondrial content. Ten patients with symptomatic peripheral arterial disease (study group) and 10 subjects without ischaemia (control group) were included. Ankle brachial index and ultrasound imaging were performed before and after vascular intervention to confirm technically successful revascularisation. Within the study group, muscle biopsies from the gastrocnemius muscle were taken before vascular intervention and six weeks after revascularisation. Within the control group, tissue was harvested once.Results: There were no significant group differences regarding anthropometric data. CSA showed a significant increase after successful revascularisation (CSA pre-operative 281.4 (252.4-391.8) nmol/min/mg protein vs. CSA post-operative 438.5 (361.4-471.3) nmol/min/mg protein; p = .01) with post-operative return of values to the range of control subjects (CSA control 396.6 (308.2-435.9)). Mitochondrial respiration normalised to CSA in oxidative phosphorylation (P) as well as in electron transfer (E) capacity were significantly reduced post-operatively when compared with pre-operative values (P pre-operative 0.218 (0.196-0.266) pmol/(secxmg) per CSA vs. post-operative 0.132 (0.116-0.150) pmol/(secxmg) per CSA, p = .007; E pre-operative 0.230 (0.195-0.279) pmol/(secxmg) per CSA vs. post-operative 0.129 (0.120-0.154) pmol/(secxmg) per CSA, p = .005) meaning a post-operative return of values to within the range of control subjects (P control 0.124 (0.080-0.155) pmol/(secxmg) per CSA; E control 0.121 (0.079-0.125) pmol/(secxmg) per CSA).Conclusion: With these results, it has been shown that the initially impaired mitochondrial function and content can normalise after revascularisation.