Abdominal aortic aneurysms: pathophysiology and clinical issues

Lattanzi, Simona

doi:10.1111/joim.13060

Cited by 14 publications

(13 citation statements)

References 10 publications

(37 reference statements)

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“…Keywords: abdominal aortic aneurysm, animal model, retroperitoneal approach, elastase, calcium chloride, beta aminopropionitrile BACKGROUND Abdominal aortic aneurysm (AAA) is one of the most challenging cardiovascular diseases and usually has no symptoms but has the risk of spontaneous dilation and rupture. Once the aneurysm ruptures, the mortality rate is as high as 80% (1). Because of its potential lethality, AAA has always been a research hotspot.…”

Section: Resultsmentioning

confidence: 99%

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Zhu

Tang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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BackgroundConstructing an ideal model of abdominal aortic aneurysm (AAA) is of great significance to elucidate its complex pathogenesis. Therefore, we introduce a new and simple method to simulate human AAA and construct a rat AAA model through a retroperitoneal approach.MethodsForty healthy adult Sprague Dawley (SD) rats were randomly divided into a control group, elastase + calcium chloride group (PPE+CaCl2), elastase group (PPE), and elastase + beta aminopropionitrile group (PPE+BAPN) according to a male-female ratio of 1:1, with 10 rats in each group. A retroperitoneal approach was used to free the infrarenal abdominal aorta in all four groups. In the PPE + CaCl2 group, 0.1 ml of elastase (approximately 5 U) was perfused into the arterial cavity for 20 min, and 1.0 mol/L calcium chloride was infiltrated out of the arterial cavity for 10 min. In the PPE group, 0.1 mL of elastase (approximately 5U) was perfused into the arterial cavity for 20 min, and normal saline was infiltrated out of arterial cavity for 10 min; the PPE + BAPN group combined with 0.3% BAPN drinking water/day on the basis of PPE group; the control group was treated with saline instead of elastase and calcium chloride. Abdominal aortic specimens were collected after 4 weeks of feeding. The diagnostic criteria of AAA were 50% dilation of the abdominal aorta or rupture of the aneurysm at 4 weeks after the operation. Histopathology, immunohistochemistry, quantitative PCR (qPCR), western blotting assay, gelatine zymogram, and other methods were used.ResultsThe operation time of the four groups was controlled at approximately 40 min, and the success rate of the operation was 100%. Survival rate: Control Group (100%) = PPE Group (100%) > PPE + CaCl2 Group (90%) > PPE + BAPN Group (40%); Aneurysm formation rate: PPE + BAPN Group (100%) > PPE + CaCl2 Group (80%) > PPE Group (60%) > Control Group (0%); Aneurysm rupture rate: PPE + BAPN group (60%) > PPE + CaCl2 group (12.5%) > PPE group (0%);Inflammatory cells (macrophages, T cells, B cells, dendritic cells) infiltrated in different degrees in the PPE + CaCl2, PPE and PPE + BAPN groups. Vascular thickness, elastic fiber content, collagen fiber content, and vascular smooth muscle cell content in the PPE + CaCl2 group and PPE + BNPA group were significantly lower than those in Control group (P < 0.05). The content of elastic fibers and vascular smooth muscle cells in the PPE group were significantly lower than that in Control group (P < 0.05). The expression and activity of matrix metalloproteinase 2 (MMP2) and MMP9 in the PPE + CaCl2 group, PPE group, and PPE + BNPA group were significantly higher than those in the control group (P < 0.05).ConclusionsA new, simple, and reproducible rat AAA model can be constructed by a retroperitoneal approach. The pathological features of the three models are effective simulation of human AAA inflammatory cell infiltration, protease activity enhancement, and extracellular matrix destruction. The PPE+ CaCl2 model has the advantages of a high survival rate, high aneurysm formation rate, good stability, and reproducibility. It is an ideal animal model for studying the pathogenesis of AAA. The PPE + BAPN model can simulate the characteristics of spontaneous rupture of aneurysms. It is an ideal animal model to study the mechanism of AAA rupture.

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Section: Resultsmentioning

confidence: 99%

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Zhu

Tang

Zhou

et al. 2022

Front. Cardiovasc. Med.

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“…At present, it is suggested that inflammation initiates the pathological process of AAA, followed by degradation of the ECM ( Lattanzi, 2020 ). However, some studies have indicated that media ECM degradation caused by various physical and chemical factors aggravates inflammation and immune cell infiltration ( Cai et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm

Wang

Kan

et al. 2022

Front. Genet.

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Background: N6-methyladenosine (m6A) is the most prevalent non-cap reversible modification present in messenger RNAs and long non-coding RNAs, and its dysregulation has been linked to multiple cardiovascular diseases, including cardiac hypertrophy and atherosclerosis. Although limited studies have suggested that m6A modification contributes to abdominal aortic aneurysm (AAA) development, the full landscape of m6A regulators that mediate modification patterns has not been revealed.Methods: To distinguish the m6A methylation subtypes in AAA patients, an unsupervised clustering method was carried out, based on the mRNA levels of 17 m6A methylation regulators. Differentially expressed genes were identified by comparing clusters. An m6Ascore model was calculated using principal component analysis and structured to assess the m6A methylation patterns of single samples. Subsequently, the relationship between the m6Ascore and immune cells and the hallmark gene set was analyzed. Finally, pairs of circRNA-m6A regulators and m6A regulators-m6A related genes were used to establish a network.Results: We identified three m6A methylation subtypes in the AAA samples. The m6Acluster A and C were characterized as more immunologically activated because of the higher abundance of immune cells than that in m6Acluster B. The m6Acluster B was less enriched in inflammatory pathways and more prevalent in pathways related to extracellular matrix stability. Subsequently, we divided the individual samples into two groups according to the m6Ascore, which suggested that a high m6Ascore predicted more active inflammatory pathways and higher inflammatory cell infiltration. A network consisting of 9 m6A regulators and 37 circRNAs was constructed.Conclusion: This work highlighted that m6A methylation modification was highly correlated with immune infiltration of AAA, which may promote the progression of AAA. We constructed an individualized m6Ascore model to provide evidence for individualized treatments in the future.

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“…The development of AAA is related to a focal dilatation of the abdominal aorta measuring 50% greater than the normal proximal segment or >3 cm in maximum diameter. The progression of AAA can lead to aneurysm rupture, an event that reaches 60–80% of mortality [ 11 , 12 , 13 , 14 , 15 ]. In turn, CVD is defined as a syndrome of chronic morphological and functional abnormalities in the venous circulation of the lower extremities, resulting from venous valve incompetence, venous reflux, and venous hypertension [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

“…In turn, CVD is defined as a syndrome of chronic morphological and functional abnormalities in the venous circulation of the lower extremities, resulting from venous valve incompetence, venous reflux, and venous hypertension [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Despite the different clinical images of these diseases, they share many common pathological conditions, including endothelial dysfunction, inflammatory response, and vascular remodeling [ 6 , 7 , 11 , 12 , 16 , 17 , 20 ]. Furthermore, the high prevalence, multifactorial character, and burden of severe life-threatening consequences of these diseases made them major global health problems [ 6 , 8 , 9 , 10 , 13 , 14 , 15 , 18 , 19 , 22 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

Zalewski

Ruszel

Stępniewski

et al. 2022

JCM

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A growing body of evidence indicates a crucial role of miRNA regulatory function in a variety of mechanisms that contribute to the development of diseases. In our previous work, alterations in miRNA expression levels and targeted genes were shown in peripheral blood mononuclear cells (PBMCs) from patients with lower extremity artery disease (LEAD), abdominal aortic aneurysm (AAA), and chronic venous disease (CVD) in comparison with healthy controls. In this paper, previously obtained miRNA expression profiles were compared between the LEAD, AAA, and CVD groups to find either similarities or differences within the studied diseases. Differentially expressed miRNAs were identified using the DESeq2 method implemented in the R programming software. Pairwise comparisons (LEAD vs. AAA, LEAD vs. CVD, and AAA vs. CVD) were performed and revealed 10, 8, and 17 differentially expressed miRNA transcripts, respectively. The functional analysis of the obtained miRNAs was conducted using the miRNet 2.0 online tool and disclosed associations with inflammation and cellular differentiation, motility, and death. The miRNet 2.0 tool was also used to identify regulatory interactions between dysregulated miRNAs and target genes in patients with LEAD, AAA, and CVD. The presented research provides new information about similarities and differences in the miRNA-dependent regulatory mechanisms involved in the pathogenesis of LEAD, AAA, and CVD.

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Abdominal aortic aneurysms: pathophysiology and clinical issues

Abstract: Click here to view the Original article by Dr. Langenskiöld et al.

Cited by 14 publications

References 10 publications

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Establishment of a New Abdominal Aortic Aneurysm Model in Rats by a Retroperitoneal Approach

Novel insight of N6-methyladenosine modified subtypes in abdominal aortic aneurysm

miRNA Regulatory Networks Associated with Peripheral Vascular Diseases

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