Nygaard Rie H, Jensen Jakob K, Voermans Nicol C, Heinemeier Katja M, Schjerling Peter, Holm Lars, Agergaard Jakob, Mackey Abigail L, Andersen Jesper L, Remvig Lars, Kjaer Michael
Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark;
Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
J Appl Physiol (1985). 2017 Aug 1;123(2):482-488. doi: 10.1152/japplphysiol.01044.2016. Epub 2017 Jun 8.
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; = 5 (Denmark)+ 8 (The Netherlands)] and vascular EDS (vEDS; = 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 ( = 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. 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.
已知患有埃勒斯-当洛综合征（EDS）的患者存在基因受损的结缔组织以及以疼痛、疲劳和痉挛形式出现的骨骼肌症状；然而，早期研究未能将这些症状与肌肉形态变化联系起来。我们获取了典型EDS患者（cEDS；丹麦5例 + 荷兰8例）和血管型EDS患者（vEDS；3例）的骨骼肌活检样本，并分析了肌纤维形态和含量（蛋白质印迹法以及肌纤维类型/面积分布）以及肌肉mRNA表达和蛋白质合成速率（逆转录-聚合酶链反应和稳定同位素技术）。cEDS患者在肌纤维类型/面积、肌球蛋白/α-肌动蛋白比率、肌肉蛋白质合成速率或mRNA表达方面与健康对照者（7 - 11例）并无差异。相比之下，与cEDS患者相比，vEDS患者的基质蛋白表达更高（纤连蛋白和基质金属蛋白酶-2）。cEDS患者的肌肉形态和蛋白质合成出人意料地正常，而与cEDS患者相比，vEDS患者骨骼肌中细胞外基质重塑的mRNA表达更高。本研究首次系统地对埃勒斯-当洛综合征患者的肌肉活检样本进行研究，重点关注肌肉结构和功能。这些患者患有严重的肌肉症状，但在我们的研究中，他们的肌肉表现出人意料地正常，这表明肌肉症状可能间接源自周围的结缔组织。这些发现具有基础生理学重要性，并对这些患者未来的物理治疗选择具有启示意义。
