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European Heart Journal Aug 2023Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in... (Review)
Review
Abdominal aortic aneurysm (AAA) causes ∼170 000 deaths annually worldwide. Most guidelines recommend asymptomatic small AAAs (30 to <50 mm in women; 30 to <55 mm in men) are monitored by imaging and large asymptomatic, symptomatic, and ruptured AAAs are considered for surgical repair. Advances in AAA repair techniques have occurred, but a remaining priority is therapies to limit AAA growth and rupture. This review outlines research on AAA pathogenesis and therapies to limit AAA growth. Genome-wide association studies have identified novel drug targets, e.g. interleukin-6 blockade. Mendelian randomization analyses suggest that treatments to reduce low-density lipoprotein cholesterol such as proprotein convertase subtilisin/kexin type 9 inhibitors and smoking reduction or cessation are also treatment targets. Thirteen placebo-controlled randomized trials have tested whether a range of antibiotics, blood pressure-lowering drugs, a mast cell stabilizer, an anti-platelet drug, or fenofibrate slow AAA growth. None of these trials have shown convincing evidence of drug efficacy and have been limited by small sample sizes, limited drug adherence, poor participant retention, and over-optimistic AAA growth reduction targets. Data from some large observational cohorts suggest that blood pressure reduction, particularly by angiotensin-converting enzyme inhibitors, could limit aneurysm rupture, but this has not been evaluated in randomized trials. Some observational studies suggest metformin may limit AAA growth, and this is currently being tested in randomized trials. In conclusion, no drug therapy has been shown to convincingly limit AAA growth in randomized controlled trials. Further large prospective studies on other targets are needed.
Topics: Male; Humans; Female; Prospective Studies; Genome-Wide Association Study; Anti-Bacterial Agents; Aneurysm, Ruptured; Aortic Aneurysm, Abdominal; Aortic Rupture
PubMed: 37387260
DOI: 10.1093/eurheartj/ehad386 -
Deutsches Arzteblatt International Oct 2020
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Humans
PubMed: 33568257
DOI: 10.3238/arztebl.2020.0811 -
Circulation Research Feb 2019Aortic aneurysms are a common vascular disease in Western populations that can involve virtually any portion of the aorta. Abdominal aortic aneurysms are much more... (Review)
Review
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 -
Journal of Molecular and Cellular... Feb 2022Rupture 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... (Review)
Review
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 -
Circulation Research Feb 2019Dissections or ruptures of aortic aneurysms remain a leading cause of death in the developed world, with the majority of deaths being preventable if individuals at risk... (Review)
Review
Dissections or ruptures of aortic aneurysms remain a leading cause of death in the developed world, with the majority of deaths being preventable if individuals at risk are identified and properly managed. Genetic variants predispose individuals to these aortic diseases. In the case of thoracic aortic aneurysm and dissections (thoracic aortic disease), genetic data can be used to identify some at-risk individuals and dictate management of the associated vascular disease. For abdominal aortic aneurysms, genetic associations have been identified, which provide insight on the molecular pathogenesis but cannot be used clinically yet to identify individuals at risk for abdominal aortic aneurysms. This compendium will discuss our current understanding of the genetic basis of thoracic aortic disease and abdominal aortic aneurysm disease. Although both diseases share several pathogenic similarities, including proteolytic elastic tissue degeneration and smooth muscle dysfunction, they also have several distinct differences, including population prevalence and modes of inheritance.
Topics: Animals; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Fibrillin-1; Humans; Multifactorial Inheritance; Penetrance
PubMed: 30763214
DOI: 10.1161/CIRCRESAHA.118.312436 -
Revue Medicale de Liege May 2018Ruptured abdominal aortic aneurysm is a cardiovascular emergency associated with a 30 day mortality as high as 70 %. However, recent progresses in the management of... (Review)
Review
Ruptured abdominal aortic aneurysm is a cardiovascular emergency associated with a 30 day mortality as high as 70 %. However, recent progresses in the management of these patients have improved the results. From a surgical point of view, endovascular methods such as balloon occlusion and endovascular repair (EVAR) in patients with suitable anatomy are recommended in order to reduce mortality.
Topics: Aortic Aneurysm, Abdominal; Aortic Rupture; Cardiac Surgical Procedures; Endovascular Procedures; Humans
PubMed: 29926569
DOI: No ID Found -
Journal of the American Heart... Dec 2021Aortic aneurysm, including thoracic aortic aneurysm and abdominal aortic aneurysm, is the second most prevalent aortic disease following atherosclerosis, representing...
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 -
The Permanente Journal 2019Abdominal aortic aneurysms (AAA) more commonly affect men than women and are estimated to affect 4% to 8% of men older that age 60 years. Mortality because of a ruptured... (Review)
Review
INTRODUCTION
Abdominal aortic aneurysms (AAA) more commonly affect men than women and are estimated to affect 4% to 8% of men older that age 60 years. Mortality because of a ruptured AAA is high, but elective repair is an effective and relatively safe intervention.
CASE PRESENTATION
A 79-year-old man came to the Emergency Department because of worsening back pain. Workup revealed a previously unknown, 10-cm aneurysm that had ruptured. Unfortunately, the patient died during emergency surgery.
DISCUSSION
A literature review of proper screening, referral timeframe, the most common surgical techniques, potential complications, and postoperative surveillance was conducted. Early detection, referral to vascular surgery, and possible open or endovascular repair are key to limiting the morbidity and mortality associated with AAA.
Topics: Aged; Aortic Aneurysm, Abdominal; Humans; Length of Stay; Male; Postoperative Complications; Risk Factors; Time Factors
PubMed: 31926569
DOI: 10.7812/TPP/18.218 -
Cell Communication and Signaling : CCS May 2023Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood....
BACKGROUND AND OBJECTIVES
Phenotypic switching in vascular smooth muscle cells (VSMCs) has been linked to aortic aneurysm, but the phenotypic landscape in aortic aneurysm is poorly understood. The present study aimed to analyse the phenotypic landscape, phenotypic differentiation trajectory, and potential functions of various VSMCs phenotypes in aortic aneurysm.
METHODS
Single-cell sequencing data of 12 aortic aneurysm samples and 5 normal aorta samples (obtained from GSE166676 and GSE155468) were integrated by the R package Harmony. VSMCs were identified according to the expression levels of ACTA2 and MYH11. VSMCs clustering was determined by the R package 'Seurat'. Cell annotation was determined by the R package 'singleR' and background knowledge of VSMCs phenotypic switching. The secretion of collagen, proteinases, and chemokines by each VSMCs phenotype was assessed. Cell‒cell junctions and cell-matrix junctions were also scored by examining the expression of adhesion genes. Trajectory analysis was performed by the R package 'Monocle2'. qPCR was used to quantify VSMCs markers. RNA fluorescence in situ hybridization (RNA FISH) was performed to determine the spatial localization of vital VSMCs phenotypes in aortic aneurysms.
RESULTS
A total of 7150 VSMCs were categorize into 6 phenotypes: contractile VSMCs, fibroblast-like VSMCs, T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs. The proportions of T-cell-like VSMCs, adipocyte-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs were significantly increased in aortic aneurysm. Fibroblast-like VSMCs secreted abundant amounts of collagens. T-cell-like VSMCs and macrophage-like VSMCs were characterized by high chemokine levels and proinflammatory effects. Adipocyte-like VSMCs and mesenchymal-like VSMCs were associated with high proteinase levels. RNA FISH validated the presence of T-cell-like VSMCs and macrophage-like VSMCs in the tunica media and the presence of mesenchymal-like VSMCs in the tunica media and tunica adventitia.
CONCLUSION
A variety of VSMCs phenotypes are involved in the formation of aortic aneurysm. T-cell-like VSMCs, macrophage-like VSMCs, and mesenchymal-like VSMCs play pivotal roles in this process. Video Abstract.
Topics: Humans; Muscle, Smooth, Vascular; In Situ Hybridization, Fluorescence; Aortic Aneurysm; Phenotype; RNA; Sequence Analysis, RNA; Myocytes, Smooth Muscle
PubMed: 37189183
DOI: 10.1186/s12964-023-01120-5 -
IUBMB Life Oct 2022Thrombospondins are a family of matricellular proteins with a multimeric structure that is known to be involved in several biological and pathological processes. Their... (Review)
Review
Thrombospondins are a family of matricellular proteins with a multimeric structure that is known to be involved in several biological and pathological processes. Their relationship with vascular disorders has raised special interest recently. Aortic aneurysms are related to the impairment of vascular remodeling, in which extracellular matrix proteins seem to play an important role. Thus, research in thrombospondins, and their potential role in aneurysm development is progressively gaining importance. Nevertheless, studies showing thrombospondin dysregulation in human samples are still scarce. Although studies performed in vitro and in vivo models are essential to understand the molecular mechanisms and pathways underlying the disorder, descriptive studies in human samples are also necessary to ascertain their real value as biomarkers and/or novel therapeutic targets. The present article reviews the latest findings regarding the role of thrombospondins in aortic aneurysm development, paying particular attention to the studies performed in human samples.
Topics: Aortic Aneurysm; Biomarkers; Extracellular Matrix Proteins; Humans; Thrombospondins
PubMed: 35293116
DOI: 10.1002/iub.2610