Abdominal Aortic Aneurysm Formation with a Focus on Vascular Smooth Muscle Cells

Qian, Guoqing; Adeyanju, O.; Olajuyin, Ayobami Matthew; Guo, Xia

doi:10.3390/life12020191

Cited by 40 publications

(28 citation statements)

References 162 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is widely acknowledged that inflammatory mediators contribute to phenotypic and functional alterations in AoSMCs during AAA development (reviewed in 41 ). Stress-triggered c ATM transcription would thus work as a signal for activating survival pathways (like BCL2 ) by fine-tuning ATM expression levels.…”

Section: Discussionmentioning

confidence: 99%

The circular RNA Ataxia-telangiectasia mutated (cATM) regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms

Fasolo

Winski

et al. 2022

Preprint

View full text Add to dashboard Cite

An abdominal aortic aneurysm (AAA) is a pathological widening of the aortic wall characterized by loss of smooth muscle cells (SMCs), extracellular matrix degradation, and local inflammation. This condition is often asymptomatic until rupture occurs, leading to high morbidity and mortality rates. Diagnosis is often accidental, and for now, the only available treatment option remains surgical intervention. Circular RNAs (circRNAs) are RNA loops that originated from backsplicing, which have received increasing attention as a novel class of functional non-coding RNAs contributing to cardiovascular physiology and disease. Their high structural stability, combined with a remarkable enrichment in body fluids, make circRNAs promising disease biomarkers. We aimed to investigate the contribution of circRNAs to AAA pathogenesis and their potential application as biomarkers for AAA diagnosis. Combined circRNA array and quantitative real-time PCR analysis revealed the presence of differentially expressed circular transcripts stemming from AAA-relevant gene loci. Among these, the circRNA to the Ataxia-telangiectasia mutated gene (cATM) was upregulated in human AAA tissue specimens, in AAA patient-derived SMCs, and serum samples collected from aneurysm patients. In control primary aortic SMCs, cATM increased upon angiotensin II stimulation, while its silencing triggered apoptosis. Furthermore, doxorubicin could induce cATM expression, supporting a link with acute stress response in SMCs. Constitutively higher cATM expressing AAA patient-derived SMCs were less vulnerable to oxidative stress-induced cell death and survival pathways enriched when compared to control SMCs. Taken together, this data supports the role of cATM in adapting SMCs to oxidative stress in the vascular AAA micromilieu. This molecular signature provides an additional parameter to be included in procedures for AAA screening in combination with already established practices.

show abstract

Section: Discussionmentioning

confidence: 99%

The circular RNA Ataxia-telangiectasia mutated (cATM) regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms

Fasolo

Winski

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…of small aneurysms continue to expand to rupture and are expected to be related to multiple factors after surgery [13, 14]. In the development of abdominal aortic aneurysm, VSMC phenotype function conversion and dysfunction, the VSMC phenotype can be converted into macrophage-like cells during the development of abdominal aortic aneurysm, and the phenotype conversion is correlated with arterial calcification and arteriosclerosis density [9].…”

Section: Discussionmentioning

confidence: 99%

“…VSMCs express proteolytic enzymes to degrade the aortic extracellular matrix. Apoptosis of VMSCs is another important factor in the development of AAA [9]. Studies have shown that knockdown of Angptl2 can inhibit the proliferation, migration and invasion of VSMCs [10].…”

Section: Introductionmentioning

confidence: 99%

Inflammation induced Vascular Smooth Muscle Cell expressing Angiopoietin-like 2 to promote the development of abdominal aortic aneurysm

Yang

Guo

et al. 2022

Preprint

View full text Add to dashboard Cite

Objective: The objective of this study is to investigate the expression of angiopoietin-like protein 2 (Angptl2) in abdominal aortic aneurysm (AAA) and the expression of Angptl2 in vascular smooth muscle cells (VSMC) under inflammation stimuli. Methods: The mouse AAA model was induced by applying calcium chloride method based the literature and the expression of Angptl2 in AAA was investigated by immunohistochemical staining. The primary VSMCs were cultured and identified following with inflammatory stimuli by Escherichia coli lipopolysaccharide (LPS) for 30 minutes and 24 hours. The expression of Angptl2 were assessed by RT-qPCR and ELISA. Results: The mouse AAA model was successfully established after being induced by calcium chloride. The inflammatory cell infiltration in the arterial tissue of the mice in the experimental group was obvious, and the elastic fiber layer was thinned and broken. Immunohistochemical staining showed that the expression of Angptl2 in AAA was up-regulated; After LPS treatment, both the mRNA and protein expressions of Angptl2 were significantly up-regulated in VSMCs in the experimental group compared with control group. Conclusion: Angptl2 expressed in VSMCs promotes the development of calcium chloride induced AAA.

show abstract

“…Moreover, elective stable abdominal aortic aneurysms (eAAAs) can be fatal. In spite of extensive literature on the pathogenesis, evolution, and rupture of AAA (13)(14)(15), prevention or suppression of AAA in a clinical setting still remains an unanswered question.…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Fu¹,

Feng²,

Zhang³

et al. 2022

Ann Transl Med

View full text Add to dashboard Cite

Background: N6-methyladenosine (m6A) is found in almost all nuclear RNAs of eukaryotes, playing an important and diverse role in many biological processes. Nonetheless, the roles of m6A regulators in abdominal aortic aneurysm (AAA) unknown. Therefore, there is a pressing need to identify m6A RNA methylation regulators in the diagnosis of AAA, determination of individualized risk, discovery of therapeutic targets, and improve understanding of pathogenesis.Methods: The GSE98278 dataset were obtained from the Gene Expression Omnibus (GEO) database to perform differential analysis of m6A-related regulators between elective stable abdominal aortic aneurysms (eAAA) and abdominal aortic aneurysm ruptured (rAAA). The random forest model was used to screen candidate m6A regulators to predict the risk of rAAA. The single sample gene set enrichment analysis (ssGSEA) method was then used to evaluate the abundance of 23 immune cells in AAA. The m6A RNA Methylation Quantification Kit was used to measure the total m6A levels of AAA and normal abdominal aorta. The terminal deoxynucleotidyl transferase mediated dUTP Nick-End Labeling (TUNEL) apoptosis assay kit was used to detect the human aortic smooth muscle cells (HASMCs) apoptotic after RBM15 knockdown. Mechanically, RBM15 knockdown was found to reduce the expression of CASP3 in an m6A-dependent manner by Western blotting, RNA immunoprecipitation (RIP), and methylated RNA immunoprecipitation-quantitative polymerase chain reaction (MeRIP-RT-PCR).Results: RBM15, WTAP, ALKBH5, and IGFBP3 were highly expressed in rAAA. In contrast, RBM15B showed opposite results (P<0.05). The high m6A level in the rAAA compared with eAAA and normal abdominal aorta (P<0.05). The random forest model was used to screen 5 candidate m6A regulators to predict the risk of rAAA. Expression of the 5 m6A methylation regulators was validated in AAA samples (P<0.05). RBM15 knockdown inhibited the apoptosis of HASMCs. RBM15 knockdown reduced the expression of CASP3 in an m6A-dependent manner. A strong correlation between the five m6A methylation regulators and immune cell infiltration was identified.Conclusions: In summary, m6A regulators play nonnegligible roles in the occurrence of rAAA. Our investigation of m6A patterns may be able to guide future immunotherapy strategies for AAA.

show abstract

Abdominal Aortic Aneurysm Formation with a Focus on Vascular Smooth Muscle Cells

Cited by 40 publications

References 162 publications

The circular RNA Ataxia-telangiectasia mutated (cATM) regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms

The circular RNA Ataxia-telangiectasia mutated (cATM) regulates oxidative stress in smooth muscle cells in expanding abdominal aortic aneurysms

Inflammation induced Vascular Smooth Muscle Cell expressing Angiopoietin-like 2 to promote the development of abdominal aortic aneurysm

Bioinformatic analyses of the role of m6A RNA methylation regulators in abdominal aortic aneurysm

Contact Info

Product

Resources

About