Targeting autophagy in aortic aneurysm and dissection

Fang, Zemin; Xiao, Feng; Chen, Yue; Luo, Hanshen; Jiang, Ding‐Sheng; Yi, Xin

doi:10.1016/j.biopha.2022.113547

Cited by 9 publications

(7 citation statements)

References 104 publications

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“…These studies on histone methylation were conducted mostly in the context of cancer and degenerative diseases, which have been shown to be closely affected by ferroptosis. Interestingly, the findings of our group and others have suggested that multiple forms of regulated cell death are involved in the development of aortic dissection (AD), and histone methylation plays a critical role in these biological processes 83,90–95 . More importantly, our recently published results revealed that ferroptosis, in particular, is involved in the development of AD 96 .…”

Section: Epigenetic Regulation In Ferroptosismentioning

confidence: 78%

“…Interestingly, the findings of our group and others have suggested that multiple forms of regulated cell death are involved in the development of aortic dissection (AD), and histone methylation plays a critical role in these biological processes. 83,[90][91][92][93][94][95] More importantly, our recently published results revealed that ferroptosis, in particular, is involved in the development of AD. 96 Furthermore, by screening multiple inhibitors of methyltransferases, we found that BRD4770 negatively regulated ferroptosis in VSMCs by inhibiting the H3K9me1/2/3 modifications.…”

Section: Histone Methylation In Ferroptosismentioning

confidence: 82%

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The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

Yang

Luo

et al. 2023

MedComm

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Ferroptosis is a form of regulated cell death triggered by the iron‐dependent peroxidation of phospholipids. Interactions of iron and lipid metabolism factors jointly promote ferroptosis. Ferroptosis has been demonstrated to be involved in the development of various diseases, such as tumors and degenerative diseases (e.g., aortic dissection), and targeting ferroptosis is expected to be an effective strategy for the treatment of these diseases. Recent studies have shown that the regulation of ferroptosis is affected by multiple mechanisms, including genetics, epigenetics, posttranscriptional modifications, and protein posttranslational modifications. Epigenetic changes have garnered considerable attention due to their importance in regulating biological processes and potential druggability. There have been many studies on the epigenetic regulation of ferroptosis, including histone modifications (e.g., histone acetylation and methylation), DNA methylation, and noncoding RNAs (e.g., miRNAs, circRNAs, and lncRNAs). In this review, we summarize recent advances in research on the epigenetic mechanisms involved in ferroptosis, with a description of RNA N6‐methyladenosine (m6A) methylation included, and the importance of epigenetic regulation in biological processes and ferroptosis‐related diseases, which provides reference for the clinical application of epigenetic regulators in the treatment of related diseases by targeting ferroptosis.

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Section: Epigenetic Regulation In Ferroptosismentioning

confidence: 78%

Section: Histone Methylation In Ferroptosismentioning

confidence: 82%

The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

Yang

Luo

et al. 2023

MedComm

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“…Autophagy is a well-conserved and self-degradation process that maintains cellular homeostasis. Accumulating evidence has revealed that autophagy is closely related to TAAD ( Fang et al, 2022 ). Previous studies have shown that autophagy is activated during TAAD formation, and that enhanced autophagy can lead to the autophagic death of VSMCs ( Li et al, 2018 ; Wang et al, 2016 ).…”

Section: Discussionmentioning

confidence: 99%

Tandem mass tag-based quantitative proteomic analysis identification of succinylation related proteins in pathogenesis of thoracic aortic aneurysm and aortic dissection

Zhang,

Wang

et al. 2023

PeerJ

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Background Thoracic aortic aneurysm and dissection (TAAD) are devastating cardiovascular diseases with a high rate of disability and mortality. Lysine succinylation, a newly found post-translational modification, has been reported to play an important role in cardiovascular diseases. However, how succinylation modification influences TAAD remains obscure. Methods Ascending aortic tissues were obtained from patients with thoracic aortic aneurysm (TAA, n = 6), thoracic aortic dissection (TAD) with pre-existing aortic aneurysm (n = 6), and healthy subjects (n = 6). Global lysine succinylation level was analyzed by Western blotting. The differentially expressed proteins (DEPs) were analyzed by tandem mass tag (TMT) labeling and mass spectrometry. Succinylation-related proteins selected from the literature review and AmiGO database were set as a reference inventory for further analysis. Then, the pathological aortic sections were chosen to verify the proteomic results by Western blotting and qRT-PCR. Results The level of global lysine succinylation significantly increased in TAA and TAD patients compared with healthy subjects. Of all proteins identified by proteomic analysis, 197 common DEPs were screened both in TAA and TAD group compared with the control group, of which 93 proteins were significantly upregulated while 104 were downregulated. Among these 197 DEPs, OXCT1 overlapped with the succinylation-related proteins and was selected as the target protein involved in thoracic aortic pathogenesis. OXCT1 was further verified by Western blotting and qRT-PCR, and the results showed that OXCT1 in TAA and TAD patients was significantly lower than that in healthy donors (p < 0.001), which was consistent with the proteomic results. Conclusions OXCT1 represents novel biomarkers for lysine succinylation of TAAD and might be a therapeutic target in the future.

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“…More and more evidence shows that autophagy plays an important role in a variety of cardiovascular diseases, such as aneurysm, aortic dissection, atherosclerosis, myocardial ischaemia‐reperfusion injury, etc. For example, knocking out ATG5 or ATG7, inhibiting autophagy and excessive activation of autophagy can promote the occurrence of aortic aneurysm and aortic dissection 16 . Using computational modelling, the current investigation identified a possible regulatory effect for the lncRNA SNHG15/miR‐153‐3p/ATG5 pathway in ischaemic.…”

Section: Introductionmentioning

confidence: 89%

“…For example, knocking out ATG5 or ATG7, inhibiting autophagy and excessive activation of autophagy can promote the occurrence of aortic aneurysm and aortic dissection. 16 Using computational modelling, the current investigation identified a possible regulatory effect for the lncRNA SNHG15/miR-153-3p/ ATG5 pathway in ischaemic. For validating our speculation, we conducted this study.…”

Section: Introductionmentioning

confidence: 97%

LncRNA SNHG15 regulates autophagy and prevents cerebral ischaemia‐reperfusion injury through mediating miR‐153‐3p/ATG5 axis

Yu,

Cai,

Zhou

2023

J Cellular Molecular Medi

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Ischaemic stroke is a common cerebrovascular disease. Long non‐coding RNA (lncRNA) of small nucleolar RNA host gene (SNHG15) has been supposedly performed a regulatory role in many diseases. Nonetheless, the function of SNHG15 in cerebral ischaemia‐reperfusion injury has not been clarified. The OGD/R of Neuro2A cells simulated the ischaemic and reperfused states of the brain. Neuro2a cell line with stable transfection of plasmid with silent expression of SNHG15 was constructed. Neuro2a cell lines transfected with miR‐153‐3p mimic (miR‐153‐3p‐mimics) and miR‐153‐3p inhibitor (miR‐153‐3p‐inhibition) were constructed. Expression of SNHG15, mi R‐200a, FOXO3 and ATG7 in mouse brain tissue and N2a cells was identified by qRT‐PCR. Western blot (WB) analysis of mouse brain tissue and Neuro2a cells revealed the presence of the proteins ATG5, Cle‐caspase‐3, Bax, Bcl‐2, LC3 II/I and P62 (WB). The representation and distribution of LC3B were observed by immunofluorescence. The death of cells was measured using a technique called flow cytometry (FACS). SNHG15 was highly expressed in cerebral ischaemia‐reperfusion injury model. Down‐regulation of SNHG15 lead to lower apoptosis rate and decreased autophagy. Dual luciferase assay and co‐immunoprecipitation (CoIP) found lncRNA SNHG15/miR‐153‐3p/ATG5. Compared to cells transfected with NC suppression, cells transfected with miR‐153‐3p‐inhibition had substantially greater overexpression of LC 3 II/I, ATG5, cle‐Caspase‐3, and Bax, as determined by a recovery experiment, the apoptosis rate was elevated, yet both P62 and Bcl‐2 were significantly lower and LC3+ puncta per cells were significantly increased. Co‐transfection of miR‐153‐3p‐inhibition and sh‐SNHG15 could reverse these results. LncRNA SNHG15 regulated autophagy and prevented cerebral ischaemia‐reperfusion injury through mediating the miR‐153‐3p/ATG5 axis.

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Targeting autophagy in aortic aneurysm and dissection

Cited by 9 publications

References 104 publications

The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

The epigenetic regulatory mechanisms of ferroptosis and its implications for biological processes and diseases

Tandem mass tag-based quantitative proteomic analysis identification of succinylation related proteins in pathogenesis of thoracic aortic aneurysm and aortic dissection

LncRNA SNHG15 regulates autophagy and prevents cerebral ischaemia‐reperfusion injury through mediating miR‐153‐3p/ATG5 axis

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