Dataset Information

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

ABSTRACT:

Background

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.

Findings

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.

Conclusions

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.

SUBMITTER: Spitznagle JC

PROVIDER: S-EPMC11308466 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Publications

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

Spitznagle Jacob C JC Kacha-Ochana Akadia A Cook-Mills Joan M JM Morgan Gabrielle A GA Pachman Lauren M LM

Pediatric rheumatology online journal 20240808 1

<h4>Background</h4>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 ...[more]

PMID: 39118148

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Project description:Background :To evaluate the impact of the duration of chronic inflammation on gene expression in skeletal muscle biopsies (MBx) from untreated children with juvenile dermatomyositis (JDM) and identify genes and biological processes associated with the disease progression, expression profiling data from 16 girls with active symptoms of JDM greater or equal to 2 months were compared with 3 girls with active symptoms less than 2 months. Results: Seventy-nine genes were differentially expressed between the groups with long or short duration of untreated disease. Genes involved in immune responses and vasculature remodeling were expressed at a higher level in muscle biopsies from children with greater or equal to 2 months of symptoms, while genes involved in stress responses and protein turnover were expressed at a lower level. Among the 79 genes, expression of 9 genes showed a significant linear regression relationship with the duration of untreated disease. Five differentially expressed genes--HLA-DQA1, smooth muscle myosin heavy chain, clustering, plexin D1 and tenomodulin--were verified by quantitative RT-PCR. The chronic inflammation of longer disease duration was also associated with increased DC-LAMP+ and BDCA2+ mature dendritic cells, identified by immunohistochemistry. Conclusions: We conclude that chronic inflammation alters the gene expression patterns in muscle of untreated children with JDM. Symptoms lasting greater or equal to 2 months were associated with dendritic cell maturation and anti-angiogenic vascular remodelling, directly contributing to disease pathophysiology. Experiment Overall Design: After obtaining informed consent, 23 girls with definite JDM were enrolled in this study prior to obtaining the MRI directed diagnostic muscle biopsy. All 23 JDM samples and 4 healthy age- and sex-matched controls were expression profiled and for first gene filtering. Only profiling data from untreated patients (19 profiles) were then analyzed statistically. Experiment Overall Design: disease duration : less than 2 months: YJD-JDM-2UA-s2,YJD-JDM-1UA-s2,YJD-JDM-16UA-s2 Experiment Overall Design: disease duration : more than 2 months:YJD-JDM-30UA-s2,YJD-JDM-19UA-s2,YJD-JDM-5UA-s2,YJD-JDM-21UA-s2,YJD-JDM-18UA-s2,YJD-JDM-3UA-s2,YJD-JDM-23UA-s2,YJD-JDM-9UA-S2,YJD-JDM-12UA-s2,YJD-JDM-14UA-s2,YJD-JDM-25UA-s2,YJD-JDM-8UA-s2,YJD-JDM-15UA-s2,YJD-JDM-13UA-s2,YJD-JDM-10UA-S2,YJD-JDM-6UA-s2.

Dataset Information

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

Background

Findings

Conclusions

Publications

Increased vascular deposition of oxidized LDL in untreated juvenile dermatomyositis.

Similar Datasets

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