Review

Authors: N Sakalihasan, R Limet, O D Defawe...

Abdominal aortic aneurysms cause 1.3% of all deaths among men aged 65-85 years in developed countries. These aneurysms are typically asymptomatic until the catastrophic event of rupture. Repair of large or symptomatic aneurysms by open surgery or endovascular repair is recommended, whereas repair of small abdominal aortic aneurysms does not provide a significant benefit. Abdominal aortic aneurysm is linked to the degradation of the elastic media of the atheromatous aorta. An inflammatory cell infiltrate, neovascularisation, and production and activation of various proteases and cytokines contribute to the development of this disorder, although the underlying mechanisms are unknown. In this Seminar, we aim to provide an updated review of the pathophysiology, current and new diagnostic procedures, assessment, and treatment of abdominal aortic aneurysm to provide family practitioners with a working knowledge of this disorder.

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Humans; Risk Factors

PubMed: 15866312
DOI: 10.1016/S0140-6736(05)66459-8

Review

Authors: Abhijit Chakraborty, Yang Li, Chen Zhang...

Rupture of aortic aneurysm and dissection (AAD) remains a leading cause of death. Progressive smooth muscle cell (SMC) loss is a crucial feature of AAD that contributes to aortic dysfunction and degeneration, leading to aortic aneurysm, dissection, and, ultimately, rupture. Understanding the molecular mechanisms of SMC loss and identifying pathways that promote SMC death in AAD are critical for developing an effective pharmacologic therapy to prevent aortic destruction and disease progression. Cell death is controlled by programmed cell death pathways, including apoptosis, necroptosis, pyroptosis, and ferroptosis. Although these pathways share common stimuli and triggers, each type of programmed cell death has unique features and activation pathways. A growing body of evidence supports a critical role for programmed cell death in the pathogenesis of AAD, and inhibitors of various types of programmed cell death represent a promising therapeutic strategy. This review discusses the different types of programmed cell death pathways and their features, induction, contributions to AAD development, and therapeutic potential. We also highlight the clinical significance of programmed cell death for further studies.

Topics: Aortic Dissection; Aortic Aneurysm; Apoptosis; Ferroptosis; Humans; Myocytes, Smooth Muscle

PubMed: 34597613
DOI: 10.1016/j.yjmcc.2021.09.010

Review

Authors: Raymundo Alain Quintana, W Robert Taylor

Aortic aneurysms are a common vascular disease in Western populations that can involve virtually any portion of the aorta. Abdominal aortic aneurysms are much more common than thoracic aortic aneurysms and combined they account for >25 000 deaths in the United States annually. Although thoracic and abdominal aortic aneurysms share some common characteristics, including the gross anatomic appearance, alterations in extracellular matrix, and loss of smooth muscle cells, they are distinct diseases. In recent years, advances in genetic analysis, robust molecular tools, and increased availability of animal models have greatly enhanced our knowledge of the pathophysiology of aortic aneurysms. This review examines the various proposed cellular mechanisms responsible for aortic aneurysm formation and identifies opportunities for future studies.

Topics: Aortic Aneurysm; Cytokines; Extracellular Matrix; Humans; Oxidative Stress; Renin-Angiotensin System

PubMed: 30763207
DOI: 10.1161/CIRCRESAHA.118.313187

Authors: Haocheng Lu, Wa Du, Lu Ren...

Aortic aneurysm, including thoracic aortic aneurysm and abdominal aortic aneurysm, is the second most prevalent aortic disease following atherosclerosis, representing the ninth-leading cause of death globally. Open surgery and endovascular procedures are the major treatments for aortic aneurysm. Typically, thoracic aortic aneurysm has a more robust genetic background than abdominal aortic aneurysm. Abdominal aortic aneurysm shares many features with thoracic aortic aneurysm, including loss of vascular smooth muscle cells (VSMCs), extracellular matrix degradation and inflammation. Although there are limitations to perfectly recapitulating all features of human aortic aneurysm, experimental models provide valuable tools to understand the molecular mechanisms and test novel therapies before human clinical trials. Among the cell types involved in aortic aneurysm development, VSMC dysfunction correlates with loss of aortic wall structural integrity. Here, we discuss the role of VSMCs in aortic aneurysm development. The loss of VSMCs, VSMC phenotypic switching, secretion of inflammatory cytokines, increased matrix metalloproteinase activity, elevated reactive oxygen species, defective autophagy, and increased senescence contribute to aortic aneurysm development. Further studies on aortic aneurysm pathogenesis and elucidation of the underlying signaling pathways are necessary to identify more novel targets for treating this prevalent and clinical impactful disease.

Topics: Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Humans; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle

PubMed: 34796717
DOI: 10.1161/JAHA.121.023601

Authors: Martin Czerny, Friedhelm Beyersdorf

Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Humans

PubMed: 33568257
DOI: 10.3238/arztebl.2020.0811

Authors: Axel Larena-Avellaneda

Topics: Humans; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Neoplasms; Blood Vessel Prosthesis Implantation

PubMed: 36617969
DOI: 10.1024/0301-1526/a001046

Authors: Yaodong Sun, Haoju Dong, Chao Sun...

OBJECTIVE

This study aims to investigate the associations between specific bacterial taxa of the gut microbiome and the development of aortic aneurysm diseases, utilizing Mendelian Randomization (MR) to explore these associations and overcome the confounding factors commonly present in observational studies.

METHODS

Employing the largest available gut microbiome and aortic aneurysm Genome-Wide Association Study databases, including MiBioGen, Dutch Microbiome Project, FinnGen, UK Biobank, and Michigan Genomics Initiative, this study performs two-sample bidirectional MR analyses. Instrumental variables, linked to microbiome taxa at significant levels, were selected for identifying relationships with abdominal aortic aneurysms (AAA), thoracic aortic aneurysms (TAA), and aortic dissection (AD). Methods like inverse variance weighted, MR-PRESSO, MR-Egger, weighted median, simple mode, and mode-based estimate were used for MR analysis. Heterogeneity was assessed with the Cochran Q test. MR-Egger regression and MR-PRESSO addressed potential unbalanced horizontal pleiotropy.

RESULTS

The analysis did not find any evidence of statistically significant associations between the gut microbiome and aortic aneurysm diseases after adjusting for the false discovery rate (FDR). Specifically, while initial results suggested correlations between 19 taxa and AAA, 25 taxa and TAA, and 13 taxa with AD, these suggested associations did not hold statistical significance post-FDR correction. Therefore, the role of individual gut microbial taxa as independent factors in the development and progression of aortic aneurysm diseases remains inconclusive. This finding underscores the necessity for larger sample sizes and more comprehensive studies to further investigate these potential links.

CONCLUSION

The study emphasizes the complex relationship between the gut microbiome and aortic aneurysm diseases. Although no statistically significant associations were found after FDR correction, the findings provide valuable insights and highlight the importance of considering gut microbiota in aortic aneurysm diseases research. Understanding these interactions may eventually contribute to identifying new therapeutic and preventive strategies for aortic aneurysm diseases.

Topics: Mendelian Randomization Analysis; Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Aortic Aneurysm, Abdominal; Aortic Aneurysm; Bacteria; Aortic Aneurysm, Thoracic; Aortic Dissection

PubMed: 39139765
DOI: 10.3389/fcimb.2024.1406845

Authors: Conrad P Hodgkinson, Jose A Gomez

Topics: Humans; Aneurysm, Ascending Aorta; Dilatation; Aortic Aneurysm; Phosphoinositide Phospholipase C

PubMed: 36897748
DOI: 10.1152/ajpheart.00687.2022

Review

Authors: Hong Lu, Alan Daugherty

Topics: Animals; Aorta, Abdominal; Aorta, Thoracic; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Disease Models, Animal; Humans; Risk Factors; Signal Transduction; Vascular Remodeling

PubMed: 28539494
DOI: 10.1161/ATVBAHA.117.309578

Review

Authors: Bo Liu, David J Granville, Jonathan Golledge...

Aortic aneurysm is a permanent focal dilation of the aorta. It is usually an asymptomatic disease but can lead to sudden death due to aortic rupture. Aortic aneurysm-related mortalities are estimated at ∼200,000 deaths per year worldwide. Because no pharmacological treatment has been found to be effective so far, surgical repair remains the only treatment for aortic aneurysm. Aortic aneurysm results from changes in the aortic wall structure due to loss of smooth muscle cells and degradation of the extracellular matrix and can form in different regions of the aorta. Research over the past decade has identified novel contributors to aneurysm formation and progression. The present review provides an overview of cellular and noncellular factors as well as enzymes that process extracellular matrix and regulate cellular functions (e.g., matrix metalloproteinases, granzymes, and cathepsins) in the context of aneurysm pathogenesis. An update of clinical trials focusing on therapeutic strategies to slow abdominal aortic aneurysm growth and efforts underway to develop effective pharmacological treatments is also provided.

Topics: Aortic Aneurysm; Disease Progression; Extracellular Matrix; Humans; Matrix Metalloproteinases; Muscle, Smooth, Vascular; Myocytes, Smooth Muscle; Vascular Remodeling

PubMed: 32083977
DOI: 10.1152/ajpheart.00621.2019