Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis

McKenzie, Erica C.; Eyrich, L.V.; Payton, Mark E.; Valberg, Stephanie J.

doi:10.1016/j.tvjl.2016.08.011

Cited by 15 publications

(16 citation statements)

References 16 publications

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“…Furthermore, a rapid widespread loss of desmin immunostaining occurs with over‐exertion rather than focal desmin aggregation . The histopathological features of Warmbloods in the present study are very similar to those described in Arabian horses with a suspected MFM which were internalised myonuclei, anguloid atrophy and distinctive desmin positive aggregates . One potential explanation for desmin staining of myofibres is muscle regeneration .…”

Section: Discussionsupporting

confidence: 78%

“…This myopathy was identified in athletic Arabian or Arabian cross horses that competed in 100 mile (161 km) endurance rides and intermittently developed signs of muscle pain and stiffness after exercise. No metabolic abnormalities were identified in the Arabian horses, but muscle biopsies revealed structural disruption of the myofibrils and ectopic accumulation of the cytoskeletal protein desmin [9,10]. The number and alignment of myofilaments is essential to muscle strength [11] and a subtle disorder affecting the number or alignment of contractile proteins could have a major impact on performance in Warmbloods competing in dressage, hunters and showjumping.…”

Section: Introductionmentioning

confidence: 96%

“…Recently, a subset of Arabian horses originally diagnosed with PSSM2 was found to have a newly identified muscle disorder termed myofibrillar myopathy (MFM) . This myopathy was identified in athletic Arabian or Arabian cross horses that competed in 100 mile (161 km) endurance rides and intermittently developed signs of muscle pain and stiffness after exercise.…”

Section: Introductionmentioning

confidence: 99%

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Clinical and histopathological features of myofibrillar myopathy in Warmblood horses

Valberg

Nicholson²,

Lewis

et al. 2017

Equine Veterinary Journal

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Summary Background To report a novel exertional myopathy, myofibrillar myopathy (MFM) in Warmblood (WB) horses. Objectives To 1) describe the distinctive clinical and myopathic features of MFM in Warmblood horses and 2) investigate the potential inheritance of MFM in a Warmblood family. Study design Retrospective selection of MFM cases and prospective evaluation of a Warmblood family. Methods Retrospectively, muscle biopsies were selected from Warmblood horses diagnosed with MFM and clinical histories obtained (n = 10). Prospectively, muscle biopsies were obtained from controls (n = 8) and a three generation WB family (n = 11). Samples were assessed for histopathology [scored 0–3], fibre types, cytoskeletal and Z disc protein aggregates, electron microscopic alterations (EM) and muscle glycogen concentrations. Results Myofibrillar myopathy-affected cases experienced exercise intolerance, reluctance to go forward, stiffness and poorly localised lameness. Abnormal aggregates of the cytoskeletal protein desmin were found in up to 120 type 2a and a few type 2x myofibres of MFM cases. Desmin positive fibres did not stain for developmental myosin, α actinin or dystrophin. Scores for internalised myonuclei (score MFM 0.83 ± 0.67, controls 0.22 ± 0.45), anguloid atrophy (MFM 0.95 ± 0.55, controls 0.31 ± 0.37) and total myopathic scores (MFM 5.85 ± 2.10, controls 1.41 ± 2.17) were significantly higher in MFM cases vs. controls. Focal Z disc degeneration, myofibrillar disruption and accumulation of irregular granular material was evident in MFM cases. Muscle glycogen concentrations were similar between MFM cases and controls. In the Warmblood family, desmin positive aggregates were found in myofibres of the founding dam and in horses from two subsequent generations. Main limitations Restricted sample size due to limited availability of well phenotyped cases. Conclusions A distinctive and potentially heritable form of MFM exists in Warmblood horses that present with exercise intolerance and abnormal hindlimb gait. Muscle tissue is characterised by ectopic accumulation of desmin and Z disc and myofibrillar degeneration.

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Section: Discussionsupporting

confidence: 78%

Section: Introductionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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Clinical and histopathological features of myofibrillar myopathy in Warmblood horses

Valberg

Nicholson²,

Lewis

et al. 2017

Equine Veterinary Journal

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“…To date, however, genetic causes of ER have not been identified in the Arabian breed. We recently identified a muscle disease with a suspected genetic predisposition in Arabian horses called myofibrillar myopathy (MFM) that causes muscle stiffness and intermittent ER (45, 63).…”

Section: Introductionmentioning

confidence: 99%

“…Approximately half of all MFM cases in human medicine are caused by mutations in genes encoding sarcomeric and extrasarcomeric proteins, including desmin, filamin C, plectin, ZASP, myotilin, αB-crystallin, and BAG3, while the remaining diseases are due to still unresolved gene defects (20, 34) Although common in humans, Arabian horses with MFM do not appear to have impaired cardiac function as they have no clinical indicators of heart failure. Even when over 20 yr of age, MFM horses complete endurance rides without abnormal elevations in heart rates that are routinely evaluated at compulsory veterinary evaluations during and after endurance races (45). The etiopathology of MFM in horses and the protein(s) or gene(s) responsible remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways

Valberg

Perumbakkam

McKenzie

et al. 2018

Physiological Genomics

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Equine myofibrillar myopathy (MFM) causes exertional muscle pain and is characterized by myofibrillar disarray and ectopic desmin aggregates of unknown origin. To investigate the pathophysiology of MFM, we compared resting and 3 h postexercise transcriptomes of gluteal muscle and the resting skeletal muscle proteome of MFM and control Arabian horses with RNA sequencing and isobaric tags for relative and absolute quantitation analyses. Three hours after exercise, 191 genes were identified as differentially expressed (DE) in MFM vs. control muscle with >1 log2 fold change (FC) in genes involved in sulfur compound/cysteine metabolism such as cystathionine-beta-synthase (CBS, ↓4.51), a cysteine and neutral amino acid membrane transporter (SLC7A10, ↓1.80 MFM), and a cationic transporter (SLC24A1, ↓1.11 MFM). In MFM vs. control at rest, 284 genes were DE with >1 log2 FC in pathways for structure morphogenesis, fiber organization, tissue development, and cell differentiation including > 1 log2 FC in cardiac alpha actin (ACTC1 ↑2.5 MFM), cytoskeletal desmoplakin (DSP ↑2.4 MFM), and basement membrane usherin (USH2A ↓2.9 MFM). Proteome analysis revealed significantly lower antioxidant peroxiredoxin 6 content (PRDX6, ↓4.14 log2 FC MFM), higher fatty acid transport enzyme carnitine palmitoyl transferase (CPT1B, ↑3.49 MFM), and lower sarcomere protein tropomyosin (TPM2, ↓3.24 MFM) in MFM vs. control muscle at rest. We propose that in MFM horses, altered cysteine metabolism and a deficiency of cysteine-containing antioxidants combined with a high capacity to oxidize fatty acids and generate ROS during aerobic exercise causes chronic oxidation and aggregation of key proteins such as desmin.

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Multifactorial and idiopathic disorders

2022

Large Animal Neurology

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Clinical, histopathological and metabolic responses following exercise in Arabian horses with a history of exertional rhabdomyolysis

Cited by 15 publications

References 16 publications

Clinical and histopathological features of myofibrillar myopathy in Warmblood horses

Clinical and histopathological features of myofibrillar myopathy in Warmblood horses

Proteome and transcriptome profiling of equine myofibrillar myopathy identifies diminished peroxiredoxin 6 and altered cysteine metabolic pathways

Multifactorial and idiopathic disorders

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