Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice

Sun, Bo; Li, Fangda; Lai, Song; Zhang, Xu; Wang, Hongxia; Li, Yuan; Wang, Wei; Chen, Yuexin; Bao, Lei; Zheng, Yuehong

doi:10.1590/acb360105

Cited by 5 publications

(5 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Transplanting bone marrow from CXCR2 −/− mice into irradiated CXCR2 +/+ mice prevents cuprizone-induced demyelination and oligodendrocyte death suggesting that the source of CXCR2 cells producing demyelination is of peripheral origins [ 238 ]. However, CXCR2 is not exclusively a marker for neutrophils as it is also expressed on CD4 + T-cells [ 266 ] and macrophages [ 267 ]. Using flow cytometry, Liu and colleagues find CXCR2 positive cells were Lymphocyte antigen 6 complex locus G6D (Ly6G) positive neutrophils [ 238 ].…”

Section: Main Textmentioning

confidence: 99%

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination

Zirngibl

Assinck

Sizov

et al. 2022

Mol Neurodegeneration

View full text Add to dashboard Cite

Background The dietary consumption of cuprizone – a copper chelator – has long been known to induce demyelination of specific brain structures and is widely used as model of multiple sclerosis. Despite the extensive use of cuprizone, the mechanism by which it induces demyelination are still unknown. With this review we provide an updated understanding of this model, by showcasing two distinct yet overlapping modes of action for cuprizone-induced demyelination; 1) damage originating from within the oligodendrocyte, caused by mitochondrial dysfunction or reduced myelin protein synthesis. We term this mode of action ‘intrinsic cell damage’. And 2) damage to the oligodendrocyte exerted by inflammatory molecules, brain resident cells, such as oligodendrocytes, astrocytes, and microglia or peripheral immune cells – neutrophils or T-cells. We term this mode of action ‘extrinsic cellular damage’. Lastly, we summarize recent developments in research on different forms of cell death induced by cuprizone, which could add valuable insights into the mechanisms of cuprizone toxicity. With this review we hope to provide a modern understanding of cuprizone-induced demyelination to understand the causes behind the demyelination in MS.

show abstract

Section: Main Textmentioning

confidence: 99%

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination

Zirngibl

Assinck

Sizov

et al. 2022

Mol Neurodegeneration

View full text Add to dashboard Cite

show abstract

“…24 Vascular inflammation is a major pathological manifestation of AAA, and macrophages participate in vascular inflammatory responses, which has been shown to be associated with increased reactive oxygen species (ROS) production, increased inflammatory factors, and increased secretion of matrix metalloproteinases (MMPs) in blood vessel matrix. 25,26 These studies indicated that macrophages and VSMCs have more complex interactions during the occurrence and development of AAA, which require further research for clarification.…”

Section: Discussionmentioning

confidence: 99%

Ferrostatin‐1 inhibits ferroptosis of vascular smooth muscle cells and alleviates abdominal aortic aneurysm formation through activating the SLC7A11/GPX4 axis

He,

Xiong,

Liu

et al. 2024

The FASEB Journal

View full text Add to dashboard Cite

Ferroptosis, a type of iron‐catalyzed necrosis, is responsible for vascular smooth muscle cell (VSMC) death and serves as a potential therapeutic target for alleviating aortic aneurysm. Here, our study explored the underlying mechanism of ferroptosis affecting VSMC functions and the resultant formation of AAA using its inhibitor Ferrostatin‐1 (Fer‐1). Microarray‐based gene expression profiling was employed to identify differentially expressed genes related to AAA and ferroptosis. An AAA model was established by angiotensin II (Ang II) induction in apolipoprotein E‐knockout (ApoE−/−) mice, followed by injection of Fer‐1 and RSL‐3 (ferroptosis inducer). Then, the role of Fer‐1 and RSL‐3 in the ferroptosis of VSMCs and AAA formation was analyzed in Ang II‐induced mice. Primary mouse VSMCs were cultured in vitro and treated with Ang II, Fer‐1, sh‐SLC7A11, or sh‐GPX4 to assess the effect of Fer‐1 via the SLC7A11/GPX axis. Bioinformatics analysis revealed that GPX4 was involved in the fibrosis formation of AAA, and there was an interaction between SLC7A11 and GPX4. In vitro assays showed that Fer‐1 alleviated Ang II‐induced ferroptosis of VSMCs and retard the consequent AAA formation. The mechanism was associated with activation of the SLC7A11/GPX4 pathway. Silencing of SLC7A11 or GPX4 could inhibit the ameliorating effect of Fer‐1 on the ferroptosis of VSMCs. In vivo animal studies further demonstrated that Fer‐1 inhibited Ang II‐induced ferroptosis and vessel wall structural abnormalities in AAA mouse through activation of the SLC7A11/GPX4 pathway. Fer‐1 may prevent AAA formation through activation of the SLC7A11/GPX4 pathway.

show abstract

“…Finally, pharmacological inhibition of CXCR2 119,120 and genetic depletion of CCR2 121 markedly reduced AngII-induced AAA formation in ApoE −/− mice.…”

Section: Cytokines Are Key Regulators Of Aaa Developmentmentioning

confidence: 91%

“…Furthermore, in murine AAA model, CXCR4 blockade by AMD3100 decreased the infiltration by adventitial macrophages, inhibited aneurysm formation, and prevented aortic-wall destruction by reducing the mRNA levels of MMP-12, MMP-14, MCP-1, MIP-1β, MIP-2α, RANTES, IL-1β, IL-6, TNF-α, and E-selectin. 118 Finally, pharmacological inhibition of CXCR2 119,120 and genetic depletion of CCR2 121 markedly reduced AngIIinduced AAA formation in ApoE −/− mice.…”

Section: Chemokine Familymentioning

confidence: 99%

Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application

et al. 2022

View full text Add to dashboard Cite

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10, IL-12, IL-17, IL-33, IL-1β, TGF-β, TNF-α, IFN-γ, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-β signaling, as well as a dual role of IL-4, IFN-γ and CXCL10, while TNF-α, IL-1β, IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-β noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AAA. Pathologic serum/plasma concentrations of IL-1β, IL-2, IL-6, TNF-α, IL-10, IL-8, IL-17, IFN-γ, and PDGF have been already found in AAA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of AAA is associated with polymorphic variants of genes encoding cytokines and their receptors: CCR2 (rs1799864), CCR5 (Delta-32), IL6 (rs1800796 and rs1800795), IL6R (rs12133641), IL10 (rs1800896), TGFB1 (rs1800469), TGFBR1 (rs1626340), TGFBR2 (rs1036095, rs4522809, rs1078985), and TNFA (rs1800629). Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-β-binding protein ( LTBP4) and an allelic variant of TGFB3 are related to a significantly slower AAA annual growth rate.

show abstract

Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice

Cited by 5 publications

References 19 publications

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination

Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination

Ferrostatin‐1 inhibits ferroptosis of vascular smooth muscle cells and alleviates abdominal aortic aneurysm formation through activating the SLC7A11/GPX4 axis

Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application

Contact Info

Product

Resources

About