Research Progress on the Pathogenesis of Aortic Aneurysm and Dissection in Metabolism

Zhou, Yihong; Wang, Tingyu; Fan, Hongyou; Liu, Shan; Teng, Xiaomei; Shao, Lianbo; Shen, Zhenya

doi:10.1016/j.cpcardiol.2023.102040

Cited by 7 publications

(4 citation statements)

References 113 publications

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“…Metabolic abnormalities are observed in both human subjects and animal models of aortic dissection [ 38 ]. Recent research indicates that metabolic disorders, specifically affecting amino acid metabolism, glucose metabolism, and lipid metabolism, play a role in the development of aortic aneurysms and dissections by impacting various functional cells within the aorta [ 39 ]. Additionally, studies have demonstrated that cellular senescence occurs prior to the onset of aortic dissection and is implicated in its pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

Qiu,

Liu,

Jiang

et al. 2024

Cardiovasc Diabetol

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Background In observational and experimental studies, diabetes has been reported as a protective factor for aortic dissection. 3-Hydroxybutyrate, a key constituent of ketone bodies, has been found to favor improvements in cardiovascular disease. However, whether the protective effect of diabetes on aortic dissection is mediated by 3-hydroxybutyrate is unclear. We aimed to investigate the causal effects of diabetes on the risk of aortic dissection and the mediating role of 3-hydroxybutyrate in them through two-step Mendelian randomization. Materials and methods We performed a two-step Mendelian randomization to investigate the causal connections between diabetes, 3-hydroxybutyrate, and aortic dissection and calculate the mediating effect of 3-hydroxybutyrate. Publicly accessible data for Type 1 diabetes, Type 2 diabetes, dissection of aorta and 3-hydroxybutyrate were obtained from genome-wide association studies. The association between Type 1 diabetes and dissection of aorta, the association between Type 2 diabetes and dissection of aorta, and mediation effect of 3-hydroxybutyrate were carried out separately. Results The IVW method showed that Type 1 diabetes was negatively associated with the risk of aortic dissection (OR 0.912, 95% CI 0.836–0.995), The weighted median, simple mode and weighted mode method showed consistent results. The mediated proportion of 3-hydroxybutyrate on the relationship between Type 1 diabetes and dissection of aorta was 24.80% (95% CI 5.12–44.47%). The IVW method showed that Type 2 diabetes was negatively associated with the risk of aortic dissection (OR 0.763, 95% CI 0.607–0.960), The weighted median, simple mode and weighted mode method showed consistent results. 3-Hydroxybutyrate does not have causal mediation effect on the relationship between Type 2 diabetes and dissection of aorta. Conclusion Mendelian randomization study revealed diabetes as a protective factor for dissection of aorta. The protective effect of type 1 diabetes on aortic dissection was partially mediated by 3-hydroxybutyrate, but type 2 diabetes was not 3-hydroxybutyrate mediated. Graphical abstract

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Section: Discussionmentioning

confidence: 99%

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

Qiu,

Liu,

Jiang

et al. 2024

Cardiovasc Diabetol

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“…Both conditions require prompt medical evaluation and management to prevent serious complications. However, despite their differences, noteworthy similarities in the pathophysiological mechanisms and clinical presentations exist ( 28 , 29 ). The study of TAA and TAD may provide more effective insights into managing and addressing these complex and interrelated cardiovascular conditions.…”

Section: Discussionmentioning

confidence: 99%

Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection

Xue,

Leng,

Zhang

et al. 2024

Exp Ther Med

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Thoracic aortic aneurysms (TAAs) are a major cause of death owing to weaker blood vessel walls and higher rupture rates in affected individuals. Vascular smooth muscle cells (VSMCs) are the predominant cell type within the aortic wall and their dysregulation may contribute to TAA progression. Enhancer of zeste homolog 2 (EZH2), a histone methyltransferase, is involved in several pathological processes; however, the biological functions and mechanisms underlying VSMC phenotype transition and vascular intimal hyperplasia remain unclear. The present study aimed to determine the involvement of EZH2 in mediating VSMC function in the development of TAAs. The expression of EZH2 was revealed to be elevated in patients with thoracic aortic dissection and TAA mouse model through western blotting and reverse transcription-quantitative PCR experiments. Subsequently, a mouse model was established using β-aminopropionitrile. In vitro , EdU labeling, Transwell assay, wound healing assay and hematoxylin-eosin staining revealed that knocking down the Ezh2 gene could reduce the proliferation, invasion, migration, and calcification of mouse primary aortic smooth muscle cells. Flow cytometry analysis found that EZH2 deficiency increased cell apoptosis. Depletion of Ezh2 in mouse primary aortic VSMCs promoted the transformation of VSMCs from a synthetic to a contractile phenotype. Using RNA-sequencing analysis, it was demonstrated that Ezh2 regulated a group of genes, including integrin β3 ( Itgb3 ), which are critically involved in the extracellular matrix signaling pathway. qChIP found Ezh2 occupies the Itgb3 promoter, thereby suppressing the expression of Itgb3 . Ezh2 promotes the invasion and calcification of VSMCs, and this promoting effect is partially reversed by co-knocking down Itgb3 . In conclusion, the present study identified a previously unrecognized EZH2-ITGB3 regulatory axis and thus provides novel mechanistic insights into the pathophysiological function of EZH2. EZH2 may thus serve as a potential target for the management of TAAs.

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“…AAD has a prevalence of up to 35 per 100,000 in people aged 65–70 years, with a high mortality rate after the onset of the disease. However, there is a lack of effective drug strategies to prevent and treat AAD (Lin et al 2023 ; Yihong Zhou et al 2024 ). The in-depth study of the disease mechanism is inevitably inseparable from animal models.…”

Section: Discussionmentioning

confidence: 99%

Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of β-Aminopropionic Nitrile as a model

Zhang,

Liang,

Zeng

et al. 2024

Animal Cells and Systems

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Aortic aneurysm/dissection (AAD) poses a life-threatening cardiovascular emergency with complex mechanisms and a notably high mortality rate. Zebrafish (Danio rerio) serve as valuable models for AAD due to the conservation of their three-layered arterial structure and genome with that of humans. However, the existing studies have predominantly focused on larval zebrafish, leaving a gap in our understanding of adult zebrafish. In this study, we utilized β-Aminopropionic Nitrile (BAPN) impregnation to induce AAD in both larval and adult zebrafish. Following induction, larval zebrafish exhibited a 28% widening of the dorsal aortic diameter ( p < 0.0004, n = 10) and aortic arch malformations, with a high malformation rate of 75% (6/8). Conversely, adult zebrafish showed a 41.67% (5/12) mortality rate 22 days post-induction. At this time point, the dorsal aortic area had expanded by 2.46 times ( p < 0.009), and the vessel wall demonstrated significant thickening (8.22 ± 2.23 μM vs. 26.38 ± 10.74 μM, p < 0.05). Pathological analysis revealed disruptions in the smooth muscle layer, contributing to a 58.33% aneurysm rate. Moreover, the expression levels of acta2, tagln, cnn1a, and cnn1b were decreased, indicating a weakened contractile phenotype. Transcriptome sequencing showed a significant overlap between the molecular features of zebrafish tissues post-BAPN treatment and those of AAD patients. Our findings present a straightforward and practical method for generating AAD models in both larval and adult zebrafish using BAPN.

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Research Progress on the Pathogenesis of Aortic Aneurysm and Dissection in Metabolism

Cited by 7 publications

References 113 publications

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

Diabetes and aortic dissection: unraveling the role of 3-hydroxybutyrate through mendelian randomization

Enhancer of zeste homolog 2 facilitates phenotypic transition of vascular smooth muscle cells leading to aortic aneurysm/dissection

Inducing aortic aneurysm/dissection in zebrafish: evaluating the efficacy of β-Aminopropionic Nitrile as a model

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