Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome

Rie H Nygaard; Jacob K Jensen; Nicol C Voermans; Katja Maria Heinemeier; Peter Schjerling; Lars Holm; Jakob Agergaard; Abigail Louise Mackey; Jesper Løvind Andersen; Lars Remvig; Michael Kjaer

doi:10.1152/japplphysiol.01044.2016

Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome

Rie H Nygaard, Jacob K Jensen, Nicol C Voermans, Katja Maria Heinemeier, Peter Schjerling, Lars Holm, Jakob Agergaard, Abigail Louise Mackey, Jesper Løvind Andersen, Lars Remvig, Michael Kjaer

2 Citations (Scopus)

Abstract

Nygaard RH, Jensen JK, Voermans NC, Heinemeier KM, Schjerling P, Holm L, Agergaard J, Mackey AL, Andersen JL, Remvig L, Kjaer M. Skeletal muscle morphology, protein synthesis, and gene expression in Ehlers-Danlos syndrome. J Appl Physiol 123: 482– 488, 2017. First published June 8, 2017; doi:10.1152/japplphysiol.01044.2016.—Patients with Ehlers-Danlos syndrome (EDS) are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue, and cramps; however earlier studies have not been able to link these symptoms to morphological muscle changes. We obtained skeletal muscle biopsies in patients with classic EDS [cEDS; n = 5 (Denmark)+ 8 (The Netherlands)] and vascular EDS (vEDS; n = 3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable isotope technique). The cEDS patients did not differ from healthy controls (n = 7–11) with regard to muscle fiber type/area, myosin/α-actin ratio, muscle protein synthesis rate, or mRNA expression. In contrast, the vEDS patients demonstrated higher expression of matrix proteins compared with cEDS patients (fibronectin and MMP-2). The cEDS patients had surprisingly normal muscle morphology and protein synthesis, whereas vEDS patients demonstrated higher mRNA expression for extracellular matrix remodeling in skeletal musculature compared with cEDS patients. NEW & NOTEWORTHY This study is the first of its kind to systematically investigate muscle biopsies from Ehlers-Danlos patients, focusing on muscle structure and function. These patients suffer from severe muscle symptoms, but in our study they show surprisingly normal muscle findings, which points toward indirect muscle symptoms originating from the surrounding connective tissue. These findings have basal physiological importance and implications for future physiotherapeutic treatment options for these patients.

Original language	English
Journal	Journal of Applied Physiology
Volume	123
Issue number	2
Pages (from-to)	482-488
ISSN	8750-7587
DOIs	https://doi.org/10.1152/japplphysiol.01044.2016
Publication status	Published - 1 Aug 2017

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@article{c117d64c5d8146f7a255f052df4c5546,

title = "Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome",

abstract = "Nygaard RH, Jensen JK, Voermans NC, Heinemeier KM, Schjerling P, Holm L, Agergaard J, Mackey AL, Andersen JL, Remvig L, Kjaer M. Skeletal muscle morphology, protein synthesis, and gene expression in Ehlers-Danlos syndrome. J Appl Physiol 123: 482– 488, 2017. First published June 8, 2017; doi:10.1152/japplphysiol.01044.2016.—Patients with Ehlers-Danlos syndrome (EDS) are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue, and cramps; however earlier studies have not been able to link these symptoms to morphological muscle changes. We obtained skeletal muscle biopsies in patients with classic EDS [cEDS; n = 5 (Denmark)+ 8 (The Netherlands)] and vascular EDS (vEDS; n = 3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable isotope technique). The cEDS patients did not differ from healthy controls (n = 7–11) with regard to muscle fiber type/area, myosin/α-actin ratio, muscle protein synthesis rate, or mRNA expression. In contrast, the vEDS patients demonstrated higher expression of matrix proteins compared with cEDS patients (fibronectin and MMP-2). The cEDS patients had surprisingly normal muscle morphology and protein synthesis, whereas vEDS patients demonstrated higher mRNA expression for extracellular matrix remodeling in skeletal musculature compared with cEDS patients. NEW & NOTEWORTHY This study is the first of its kind to systematically investigate muscle biopsies from Ehlers-Danlos patients, focusing on muscle structure and function. These patients suffer from severe muscle symptoms, but in our study they show surprisingly normal muscle findings, which points toward indirect muscle symptoms originating from the surrounding connective tissue. These findings have basal physiological importance and implications for future physiotherapeutic treatment options for these patients.",

author = "Nygaard, {Rie H} and Jensen, {Jacob K} and Voermans, {Nicol C} and Heinemeier, {Katja Maria} and Peter Schjerling and Lars Holm and Jakob Agergaard and Mackey, {Abigail Louise} and Andersen, {Jesper L{\o}vind} and Lars Remvig and Michael Kjaer",

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doi = "10.1152/japplphysiol.01044.2016",

language = "English",

volume = "123",

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T1 - Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome

AU - Nygaard, Rie H

AU - Jensen, Jacob K

AU - Voermans, Nicol C

AU - Heinemeier, Katja Maria

AU - Schjerling, Peter

AU - Holm, Lars

AU - Agergaard, Jakob

AU - Mackey, Abigail Louise

AU - Andersen, Jesper Løvind

AU - Remvig, Lars

AU - Kjaer, Michael

PY - 2017/8/1

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N2 - Nygaard RH, Jensen JK, Voermans NC, Heinemeier KM, Schjerling P, Holm L, Agergaard J, Mackey AL, Andersen JL, Remvig L, Kjaer M. Skeletal muscle morphology, protein synthesis, and gene expression in Ehlers-Danlos syndrome. J Appl Physiol 123: 482– 488, 2017. First published June 8, 2017; doi:10.1152/japplphysiol.01044.2016.—Patients with Ehlers-Danlos syndrome (EDS) are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue, and cramps; however earlier studies have not been able to link these symptoms to morphological muscle changes. We obtained skeletal muscle biopsies in patients with classic EDS [cEDS; n = 5 (Denmark)+ 8 (The Netherlands)] and vascular EDS (vEDS; n = 3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable isotope technique). The cEDS patients did not differ from healthy controls (n = 7–11) with regard to muscle fiber type/area, myosin/α-actin ratio, muscle protein synthesis rate, or mRNA expression. In contrast, the vEDS patients demonstrated higher expression of matrix proteins compared with cEDS patients (fibronectin and MMP-2). The cEDS patients had surprisingly normal muscle morphology and protein synthesis, whereas vEDS patients demonstrated higher mRNA expression for extracellular matrix remodeling in skeletal musculature compared with cEDS patients. NEW & NOTEWORTHY This study is the first of its kind to systematically investigate muscle biopsies from Ehlers-Danlos patients, focusing on muscle structure and function. These patients suffer from severe muscle symptoms, but in our study they show surprisingly normal muscle findings, which points toward indirect muscle symptoms originating from the surrounding connective tissue. These findings have basal physiological importance and implications for future physiotherapeutic treatment options for these patients.

AB - Nygaard RH, Jensen JK, Voermans NC, Heinemeier KM, Schjerling P, Holm L, Agergaard J, Mackey AL, Andersen JL, Remvig L, Kjaer M. Skeletal muscle morphology, protein synthesis, and gene expression in Ehlers-Danlos syndrome. J Appl Physiol 123: 482– 488, 2017. First published June 8, 2017; doi:10.1152/japplphysiol.01044.2016.—Patients with Ehlers-Danlos syndrome (EDS) are known to have genetically impaired connective tissue and skeletal muscle symptoms in form of pain, fatigue, and cramps; however earlier studies have not been able to link these symptoms to morphological muscle changes. We obtained skeletal muscle biopsies in patients with classic EDS [cEDS; n = 5 (Denmark)+ 8 (The Netherlands)] and vascular EDS (vEDS; n = 3) and analyzed muscle fiber morphology and content (Western blotting and muscle fiber type/area distributions) and muscle mRNA expression and protein synthesis rate (RT-PCR and stable isotope technique). The cEDS patients did not differ from healthy controls (n = 7–11) with regard to muscle fiber type/area, myosin/α-actin ratio, muscle protein synthesis rate, or mRNA expression. In contrast, the vEDS patients demonstrated higher expression of matrix proteins compared with cEDS patients (fibronectin and MMP-2). The cEDS patients had surprisingly normal muscle morphology and protein synthesis, whereas vEDS patients demonstrated higher mRNA expression for extracellular matrix remodeling in skeletal musculature compared with cEDS patients. NEW & NOTEWORTHY This study is the first of its kind to systematically investigate muscle biopsies from Ehlers-Danlos patients, focusing on muscle structure and function. These patients suffer from severe muscle symptoms, but in our study they show surprisingly normal muscle findings, which points toward indirect muscle symptoms originating from the surrounding connective tissue. These findings have basal physiological importance and implications for future physiotherapeutic treatment options for these patients.

U2 - 10.1152/japplphysiol.01044.2016

DO - 10.1152/japplphysiol.01044.2016

M3 - Journal article

C2 - 28596275

SN - 8750-7587

VL - 123

SP - 482

EP - 488

JO - Journal of Applied Physiology

JF - Journal of Applied Physiology

IS - 2

ER -

Skeletal muscle morphology, protein synthesis and gene expression in Ehlers Danlos Syndrome

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