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. 2024 Jun 1;14(1):12609.
doi: 10.1038/s41598-024-63626-3.

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants

Dylan Wilburn  1 , Dimitrios Miserlis  2   3 , Emma Fletcher  1 , Evlampia Papoutsi  1 , Ahmed Ismaeel  4 , Cassandra Bradley  1 , Andrew Ring  1 , Trevor Wilkinson  1 , Robert S Smith  5 , Lucas Ferrer  2 , Gleb Haynatzki  6 , Peter Monteleone  7 , Subhash Banerjee  8 , Elizabeth Brisbois  9 , William T Bohannon  5 , Panagiotis Koutakis  10
Affiliations

Skeletal muscle desmin alterations following revascularization in peripheral artery disease claudicants

Dylan Wilburn et al. Sci Rep. .

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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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Desmin immunofluorescence staining from patients with PAD that improved after revascularization operation. At pre-revascularization (A-B, 20 × objective) disorganization of desmin is evident with areas of higher concentration within the myofiber (C-D, 40 × objective). After post-revascularization (E–F, 20 × objective) desmin concentration within the myofiber is decreased. Subsarcolemmal desmin is mainly evident (G-H, 40 × objective) indicating a relative normal staining. Myofiber morphology is improved with myofibers having a similar shape and size after revascularization operations. Scale bars are 20 × objective at 50 μm and 40 × objective at 25 μm. Desmin is stained with green and nuclei with blue.
Figure 2
Figure 2
Desmin immunofluorescence staining from patients with PAD that did not improve after revascularization operation. At pre-revascularization (A-B, 20 × objective), the disorganization of desmin is evident in several areas of higher concentration within the myofiber (C-D, 40 × objective). After post-revascularization (E–F, 20 × objective), desmin concentration within the myofiber did not decrease. Myofiber morphology did not improve, with myofibers having irregular shape and size after revascularization operations. Scale bars are 20 × objective at 50 μm and 40 × objective at 25 μm. Desmin is stained green, and the nuclei are blue.
Figure 3
Figure 3
Revascularization operations improved mitochondrial respiration of the electron transport chain complexes I-IV. Mitochondrial respiration is normalized to citrate synthase activity. *p < 0.05.
Figure 4
Figure 4
Revascularization operations improved the walking function of patients with PAD. Six minute walking distance (SMWD), claudication onset time (COT), claudication onset distance (COD), maximum walking time (MWT), and maximum walking distance (MWD) were all significantly improved post-revascularization. *p < 0.05.
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