Division of Pediatric Rheumatology, Children's Hospital Los Angeles, 4560 Sunset Blvd., #60, Los Angeles, CA, 90027, USA.
Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Pediatr Rheumatol Online J. 2024 Aug 8;22(1):73. doi: 10.1186/s12969-024-01001-2.
Juvenile dermatomyositis (JDM) is a systemic vasculopathy associated with metabolic derangements and possible increased risk for premature atherosclerosis. Oxidation of low-density lipoprotein (LDL) in the endothelium is an early step in atherosclerotic plaque formation. It is not known if oxidized LDL is altered in children with untreated JDM. The deposition of oxidized LDL in the vasculature of muscle biopsies (MBx) from patients with untreated JDM and pediatric controls was assessed.
Frozen tissue sections of MRI-directed MBx from 20 female children with untreated JDM and 5 female controls were stained with DAPI and fluorescently labeled antibodies against von Willebrand factor (vWF) and LDL oxidized by copper (oxLDL). Blood vessels were identified by positive vWF staining, and total fluorescence of oxLDL within the vessel walls was measured. Children with untreated JDM had increased deposition of oxLDL in the walls of muscle vasculature compared to healthy children (difference in means ± SEM = 19.86 ± 8.195, p = 0.03). Within the JDM cohort, there was a trend towards increased oxLDL deposition with longer duration of untreated disease (r = 0.43, p = 0.06). There was no significant correlation found between oxLDL deposition and markers of acute JDM disease activity including disease activity scores or muscle enzymes.
This study found increased deposition of oxLDL within blood vessels of children with untreated JDM supporting the concern that these children are at increased risk for premature atherosclerosis from chronic exposure to vascular oxLDL. This study highlights the importance of early diagnosis and treatment initiation to ameliorate cardiovascular damage.
幼年型皮肌炎（JDM）是一种与代谢紊乱有关的系统性血管病变，可能增加早发动脉粥样硬化的风险。血管内皮中低密度脂蛋白（LDL）的氧化是动脉粥样硬化斑块形成的早期步骤。目前尚不清楚未经治疗的 JDM 患儿的 LDL 是否发生氧化。本研究评估了未经治疗的 JDM 患儿和儿科对照者肌肉活检（MBx）中氧化型 LDL 的沉积情况。
对 20 名未经治疗的 JDM 女性患儿和 5 名女性对照者的 MRI 引导下 MBx 的冰冻组织切片进行 DAPI 染色，并使用荧光标记的抗血管性血友病因子（vWF）和铜氧化的 LDL（oxLDL）抗体进行染色。血管通过阳性 vWF 染色进行鉴定，并测量血管壁内 oxLDL 的总荧光强度。与健康儿童相比，未经治疗的 JDM 患儿的肌肉血管壁中 oxLDL 的沉积增加（平均值差异 ± SEM = 19.86 ± 8.195，p = 0.03）。在 JDM 队列中，oxLDL 沉积与未治疗疾病的持续时间呈正相关（r = 0.43，p = 0.06）。然而，并未发现 oxLDL 沉积与 JDM 疾病活动的急性标志物（包括疾病活动评分或肌肉酶）之间存在显著相关性。
本研究发现未经治疗的 JDM 患儿血管内 oxLDL 沉积增加，提示这些患儿由于长期接触血管 oxLDL，可能会增加早发动脉粥样硬化的风险。本研究强调了早期诊断和治疗启动以改善心血管损伤的重要性。
