Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

Kilinc, Yasemin Baranoglu; Kilinc, Erkan; Danis, Aysegul; Hanci, Fatma; Turay, Sevim; Ozge, Aynur; Bolay, Hayrunnisa

doi:10.1111/head.14618

Cited by 9 publications

(3 citation statements)

References 41 publications

(84 reference statements)

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“…Cluster 1, which expressed higher RTM markers, was similar to the previously described Timd4+ or Folr2+ cluster ( 21 , 24 ). In contrast, Cluster 3 highly expressed inflammation-related genes (Ccl2, Ccl7, Ccl12), endoplasmic reticulum stress-related genes (Phlda3 and C5ar1) ( 43 , 44 ), mitochondrial metabolism-related marker (Gdf15) ( 45 ), and cell cycle arrest and senescence biomarker (Cdkn1a) ( 46 , 47 ). Therefore, we named Cluster 1 RTM Lyve1 high Mac and named Cluster 3 Cdkn1a high C5ar1 high Mac based on their characteristic genes.…”

Section: Resultsmentioning

confidence: 99%

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing

Cao,

Wu,

Wang

et al. 2024

Front. Immunol.

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PurposeA mouse model of irradiation (IR)-induced heart injury was established to investigate the early changes in cardiac function after radiation and the role of cardiac macrophages in this process.MethodsCardiac function was evaluated by heart-to-tibia ratio, lung-to-heart ratio and echocardiography. Immunofluorescence staining and flow cytometry analysis were used to evaluate the changes of macrophages in the heart. Immune cells from heart tissues were sorted by magnetic beads for single-cell RNA sequencing, and the subsets of macrophages were identified and analyzed. Trajectory analysis was used to explore the differentiation relationship of each macrophage subset. The differentially expressed genes (DEGs) were compared, and the related enriched pathways were identified. Single-cell regulatory network inference and clustering (SCENIC) analysis was performed to identify the potential transcription factors (TFs) which participated in this process.ResultsCardiac function temporarily decreased on Day 7 and returned to normal level on Day 35, accompanied by macrophages decreased and increased respectively. Then, we identified 7 clusters of macrophages by single-cell RNA sequencing and found two kinds of stage specific macrophages: senescence-associated macrophage (Cdkn1ahighC5ar1high) on Day 7 and interferon-associated macrophage (Ccr2highIsg15high) on Day 35. Moreover, we observed cardiac macrophages polarized over these two-time points based on M1/M2 and CCR2/major histocompatibility complex II (MHCII) expression. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses suggested that macrophages on Day 7 were characterized by an inflammatory senescent phenotype with enhanced chemotaxis and inflammatory factors, while macrophages on Day 35 showed enhanced phagocytosis with reduced inflammation, which was associated with interferon-related pathways. SCENIC analysis showed AP-1 family members were associated with IR-induced macrophages changes.ConclusionWe are the first study to characterize the diversity, features, and evolution of macrophages during the early stages in an IR-induced cardiac injury animal model.

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Section: Resultsmentioning

confidence: 99%

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing

Cao,

Wu,

Wang

et al. 2024

Front. Immunol.

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“…HIF-1α regulates mitochondrial function and metabolism, and adaptation to hypoxic conditions. Migraine attacks were recently shown to be accompanied by elevated HIF-1α, FGF-21, GDF-15, CGRP, and PACAP-38 in medication-naïve children with migraine [ 38 ]. HIF-1α levels were elevated in CM patients with MOH compared to EM patients and healthy controls in our study.…”

Section: Discussionmentioning

confidence: 99%

“…HIF-1α levels were elevated in CM patients with MOH compared to EM patients and healthy controls in our study. An increase in HIF-1α may be associated with mitochondrial distress and inflammation in chronic migraine [ 38 ]. Stimulation of primary glial and meningeal cell cultures with nitroglycerin, a headache trigger in migraineurs, was shown to alter intracellular iron trafficking which might have an impact on oxidative stress [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation

Vuralli,

Ceren Akgor,

Gok Dagidir

et al. 2024

J Headache Pain

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Objective Medication overuse headache (MOH) was recently shown to be associated with leaky gut in rodents. We aimed to investigate whether chronic migraine (CM) patients with MOH have elevated lipopolysaccharide levels and inflammatory molecules in blood circulation. Materials and methods The study included women participants (40 CM patients with NSAID overuse headache, 35 episodic migraine (EM) patients, and 20 healthy non-headache sufferers). Migraine duration, monthly migraine headache days, MigSCog, HADS-D, HADS-A, and HIT-6 scores were recorded. Serum samples were collected to measure circulating LPS, LPS binding protein (LBP), tight junction protein occludin, adherens junction protein vascular endothelial cadherin (VE-cadherin), CGRP, HMGB1, HIF-1α, IL-6, and IL-17 levels. Results Serum LPS, VE-Cadherin, CGRP, HIF-1α, and IL-6 levels were significantly higher in the CM + MOH group compared to the EM group and healthy controls while serum LBP and HMGB1 were higher in the CM + MOH group compared to healthy controls. IL-17 and occludin levels were comparable between the three groups. Serum HMGB1 levels in EM patients were higher compared to the control group. Mig-SCog and HIT-6 scores were higher in the CM + MOH group compared to EM patients. HADS-A and HADS-D scores were significantly higher in the CM + MOH group compared to EM patients and healthy controls, and they were also higher in EM patients compared to healthy subjects. LPS levels were correlated with VE-cadherin and occludin levels. The number of monthly migraine headache days was positively correlated with serum LPS, HIF-1α, VE-cadherin, and IL-6 levels, HADS-A, HADS-D, HIT-6, and MigSCog scores. Conclusion We have evidence for the first time that CM + MOH is associated with elevated serum LPS and LBP levels suggestive of LPS leak into the systemic circulation. Higher levels of nociceptive and/or pro-inflammatory molecules such as HMGB1, HIF-1α, IL-6, and CGRP may play a role in trigeminal sensitization and neurobiology of MOH. Intestinal hyperpermeability and consequent inflammatory response should be considered as a potential contributory factor in patients with MOH. Graphical Abstract

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Microbial Players: Unveiling the Role of Gut Microbiome in Migraine

Pandey,

Tiwari

2024

Management of Migraine Pain

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Mitochondrial metabolism related markers GDF‐15, FGF‐21, and HIF‐1α are elevated in pediatric migraine attacks

Cited by 9 publications

References 41 publications

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing

Elucidating the changes in the heterogeneity and function of radiation-induced cardiac macrophages using single-cell RNA sequencing

Lipopolysaccharide, VE-cadherin, HMGB1, and HIF-1α levels are elevated in the systemic circulation in chronic migraine patients with medication overuse headache: evidence of leaky gut and inflammation

Microbial Players: Unveiling the Role of Gut Microbiome in Migraine

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