Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages

Gong, Zhongying; Zhan, Daqiang; Nie, Meng; Li, Xiaochun; Gao, Chuang; Liu, Xuanhui; Xiang, Tangtang; Yuan, Jiangyuan; Jiang, Weiwei; Huang, Jinhao; Quan, Wei; Wang, Dong; Tian, Ye; Yuan, Hengjie; Zhang, Jianning; Jiang, Rongcai

doi:10.1186/s12974-021-02257-1

Cited by 12 publications

(8 citation statements)

References 54 publications

(93 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, beyond the hypolipidemic property, recent studies have also demonstrated that ATV has neuroprotective effects as the result of anti-inflammatory, antioxidant, and immunomodulatory activities [15][16][17]. Meanwhile, in our previous study [7], ATV can be detected in the hematoma fluid in CSDH patients and the concentration up to 40 ng/mL, thus raising the question of whether or not ATV can penetrate the blood-brain barrier (BBB). A hematoma is an encapsulated collection of fluid, blood, and blood degradation products layered between the arachnoid and dura mater.…”

Section: Discussionmentioning

confidence: 87%

See 1 more Smart Citation

Dexamethasone changes the disposition of atorvastatin by targeting the LXRα-OATP1B1 pathway

Zhan

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

Chronic subdural hematoma (CSDH) is one of the most common neurological disorders. In recent years, atorvastatin (ATV) combined with dexamethasone (DXM) has been proved to be a more efficacious therapy in treating patients with CSDH than ATV monotherapy. To investigate whether DXM has an effect on the pharmacokinetics of ATV, the expression of organic anion transport polypeptides 1B1 (OATP1B1) and upstream nuclear receptors liver X receptor α (LXRα) in rat liver and HepG2 cells were evaluated. The results showed that when DXM was combined with ATV, the area under curve (AUC(0~∞)) of ATV, o-ATV and p-ATV was increased by 1.550, 1.420, 1.676 times, respectively. In HepG2 cells, DXM inhibited the uptake of ATV by 59.24%. Also, DXM decreased the expression of OATP1B1 and LXRα both in the rat liver and HepG2 cells. Dual-luciferase reporter assay indicated that DXM had an inhibitory effect on the LXRα-OATP1B1 pathway. In conclusion, DXM downregulated the protein expression of OATP1B1 by inhibiting the LXRα-OATP1B1 pathway, thus, decreasing hepatic drug uptake and increasing plasma concentration of ATV and its active metabolites.

show abstract

Section: Discussionmentioning

confidence: 87%

“…Our previous study has demonstrated that DXM can enhance the anti-inflammatory and -angiogenic activities of ATV by increasing the ATV level in hematoma fluid and serum and by regulating the functions of macrophages [7]. However, the underlying mechanism of how DXM increases the presence of ATV in hematoma fluid and serum is still unknown.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone changes the disposition of atorvastatin by targeting the LXRα-OATP1B1 pathway

Zhan

Wang

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that it may inhibit angiogenesis by reducing inflammatory reactions in tissue. 32 In keloid, dexamethasone can effectively inhibit the expression of VEGF and the proliferation of fibroblasts. 33 Another study demonstrates that dexamethasone can inhibit the expression of VCAM-1 in rats.…”

Section: Discussionmentioning

confidence: 99%

Integration of single‐cell and bulk transcriptomics reveals immune‐related signatures in keloid

Wang

Zhou

Xie

et al. 2023

J of Cosmetic Dermatology

View full text Add to dashboard Cite

Background Keloid is a pathological dermatological condition that manifests as an overgrowth scar secondary to skin trauma. This study endeavored to excavate immune‐related signatures of keloid based on single‐cell RNA (scRNA) sequencing data and bulk RNA sequencing data. Method The keloid‐relevant scRNA sequencing dataset GSE163973 and bulk RNA sequencing dataset GSE113619 were mined from the GEO database. The “Seurat” R package was utilized for data quality control, cell clustering, and investigation of marker genes of each cell cluster. The “SingleR” package helped match the marker genes of the corresponding cluster to specific cell types. Moreover, the R package “Monocle” was deployed for pseudotemporal ordering analysis, and the “clusterProfiler” was applied for functional and pathway enrichment analysis. The immune‐related signatures were then identified, and potential targeted drugs were predicted via the DGIdb database. Verification of the immune‐related signatures in clinical validation samples was implemented by RT‐qPCR. Results Totally 23 cell clusters were screened and classified into 10 cell types based on the scRNA sequencing data. The keloid group had a significantly higher endothelial cell proportion than the control group. As enrichment analysis was applied in both differentially expressed genes (DEGs) of scRNA and bulk RNA sequencing data, we found they were enriched in multiple common immune‐related pathways and biological processes. Meanwhile, we acquired three immune‐related signatures (VCAM1, CALCRL, and HLA‐DPB1) by intersecting the above DEGs with immune‐related genes (IRGs). Then, we predicted 16 drugs potentially targeting the biomarkers through the DGIdb database. Finally, the outcome of RT‐qPCR of clinical validation samples further verified the results. Conclusion In conclusion, we analyzed the cell types and functional differences in the keloid through scRNA and bulk RNA sequencing data. We identified three immune‐related signatures (VCAM1, CALCRL, and HLA‐DPB1) in keloid, providing a basis for further in‐depth investigation of the molecular mechanisms of keloid and exploration of therapeutic targets.

show abstract

“…In fact, there is increasing evidence to have proven the efficacy of atorvastatin in treating CSDH in recent years. [19,20,22,24,39,40] Atorvastatin can increase circulating endothelial progenitor cells (EPCs) and regulatory T cells (Tregs), promote vessel repair and improve neural function. [41,42] In animal models, [9,[41][42][43] atorvastatin reduces hematoma primarily by suppressing local inflammation, can lower TNF-α and IL-6 levels and can decrease the expression of the VEGF gene .…”

Section: Discussionmentioning

confidence: 99%

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma

Xu,

Tang,

Liu

et al. 2023

Medicine

View full text Add to dashboard Cite

To explore the clinical efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma. We conducted a retrospective study to analyze the clinical data of patients with chronic subdural hematoma. Patients receiving atorvastatin treatment after surgery were divided into the study group while others were divided into the control group. As the primary outcome, we compared the hematoma recurrence rate. The secondary outcomes were the remaining volume of hematoma and the activities of daily living (Barthel index) score at 3 months after discharge. A total of 53 patients were included in the study: 30 patients in the study group (n = 30) and 23 patients in the control group (n = 23). The baseline clinical data were similar in the 2 groups (P > .05). Four patients had recurrence of hematoma in the study group, while 5 patients had recurrence of hematoma in the control group [4/30 (13.3%) versus 5/23 (21.7%), P = .661] at 3 months after discharge. The mean remaining volume of hematoma was 12.10 ± 8.80 mL in the study group and 17.30 ± 9.50 mL in the control group at 3 months after discharge, respectively. The remaining volume of hematoma in the study group was less than that in the control group (P = .045).The activities of daily living score in the study group were higher than those in the control group (97.83 ± 4.48 vs 94.78 ± 5.73, P = .034) at 3 months after discharge. Atorvastatin administration after surgery barely reduce the recurrence rate of chronic subdural hematoma, however, reduced the remaining volume of hematoma and improved neurological function.

show abstract

Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages

Cited by 12 publications

References 54 publications

Dexamethasone changes the disposition of atorvastatin by targeting the LXRα-OATP1B1 pathway

Dexamethasone changes the disposition of atorvastatin by targeting the LXRα-OATP1B1 pathway

Integration of single‐cell and bulk transcriptomics reveals immune‐related signatures in keloid

Efficacy of atorvastatin administration after surgery in patients with chronic subdural hematoma

Contact Info

Product

Resources

About