Walking performance is positively correlated to calf muscle fiber size in peripheral artery disease subjects, but fibers show aberrant mitophagy: an observational study
| Autor: | Luigi Ferrucci, Melina R. Kibbe, S H White, Ying Gao, Lihui Zhao, Robert L. Sufit, Kate Kosmac, Michael H. Criqui, Charlotte A. Peterson, Alex W. Bugg, Mary M. McDermott, Lu Tian, Marta Gonzalez-Freire, Christiaan Leeuwenburgh |
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| Rok vydání: | 2016 |
| Předmět: |
Male
Messenger Walking 030204 cardiovascular system & hematology Mitochondrion Cardiovascular Medical and Health Sciences 0302 clinical medicine Mitophagy Medicine Calf muscle Medicine(all) Core (anatomy) biology Succinate dehydrogenase General Medicine Anatomy Skeletal Mitochondria Succinate Dehydrogenase medicine.anatomical_structure Female Microtubule-Associated Proteins Oxidation-Reduction medicine.medical_specialty Immunology Oxidative phosphorylation Muscle Fibers General Biochemistry Genetics and Molecular Biology 03 medical and health sciences Peripheral Arterial Disease Clinical Research Lysosome Internal medicine Humans Aged Peripheral artery disease Biochemistry Genetics and Molecular Biology(all) business.industry Research Autophagy Skeletal muscle Mitochondrial Degradation Capillaries Endocrinology biology.protein RNA Fiber type business 030217 neurology & neurosurgery |
| Zdroj: | Journal of translational medicine, vol 14, iss 1 Journal of Translational Medicine |
| Popis: | Background Patients with lower extremity peripheral artery disease (PAD) have decreased mobility, which is not fully explained by impaired blood supply to the lower limb. Additionally, reports are conflicted regarding fiber type distribution patterns in PAD, but agree that skeletal muscle mitochondrial respiration is impaired. Methods To test the hypothesis that reduced muscle fiber oxidative activity and type I distribution are negatively associated with walking performance in PAD, calf muscle biopsies from non-PAD (n = 7) and PAD participants (n = 26) were analyzed immunohistochemically for fiber type and size, oxidative activity, markers of autophagy, and capillary density. Data were analyzed using analysis of covariance. Results There was a wide range in fiber type distribution among subjects with PAD (9–81 % type I fibers) that did not correlate with walking performance. However, mean type I fiber size correlated with 4-min normal- and fastest-paced walk velocity (r = 0.4940, P = 0.010 and r = 0.4944, P = 0.010, respectively). Although intensity of succinate dehydrogenase activity staining was consistent with fiber type, up to 17 % of oxidative fibers were devoid of mitochondria in their cores, and the core showed accumulation of the autophagic marker, LC3, which did not completely co-localize with LAMP2, a lysosome marker. Conclusions Calf muscle type I fiber size positively correlates with walking performance in PAD. Accumulation of LC3 and a lack of co-localization of LC3 with LAMP2 in the area depleted of mitochondria in PAD fibers suggests impaired clearance of damaged mitochondria, which may contribute to reduced muscle oxidative capacity. Further study is needed to determine whether defective mitophagy is associated with decline in function over time, and whether interventions aimed at preserving mitochondrial function and improving autophagy can improve walking performance in PAD. Electronic supplementary material The online version of this article (doi:10.1186/s12967-016-1030-6) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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