Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants

外周动脉疾病跛行患者血运重建后骨骼肌结蛋白的改变

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作者:Dylan Wilburn, Dimitrios Miserlis, Emma Fletcher, Evlampia Papoutsi, Ahmed Ismaeel, Cassandra Bradley, Andrew Ring, Trevor Wilkinson, Robert S Smith, Lucas Ferrer, Gleb Haynatzki, Peter Monteleone, Subhash Banerjee, Elizabeth Brisbois, William T Bohannon, Panagiotis Koutakis

Abstract

Peripheral artery disease (PAD) is characterized by varying severity of arterial stenosis, exercise induced claudication, malperfused tissue precluding normal healing and skeletal muscle dysfunction. Revascularization interventions improve circulation, but post-reperfusion changes within the skeletal muscle are not well characterized. This study investigates if revascularization enhanced hemodynamics increases walking performance with concurrent improvement of mitochondrial function and reverses abnormal skeletal muscle morphological features that develop with PAD. Fifty-eight patients completed walking performance testing and muscle biopsy before and 6 months after revascularization procedures. Muscle fiber morphology, desmin structure, and mitochondria respiration assessments before and after the revascularization were evaluated. Revascularization improved limb hemodynamics, walking function, and muscle morphology. Qualitatively not all participants recovered normal structural architecture of desmin in the myopathic myofibers after revascularization. Heterogenous responses in the recovery of desmin structure following revascularization may be caused by other underlying factors not reversed with hemodynamic improvements. Revascularization interventions clinically improve patient walking ability and can reverse the multiple subcellular functional and structural abnormalities in muscle cells. Further study is needed to characterize desmin structural remodeling with improvements in skeletal muscle morphology and function.

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