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Free Radical Biology & Medicine Nov 2022Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen...
BACKGROUND
Increasing evidence indicates that redox stress participates in MFS aortopathy, though its mechanistic contribution is little known. We reported elevated reactive oxygen species (ROS) formation and NADPH oxidase NOX4 upregulation in MFS patients and mouse aortae. Here we address the contribution of xanthine oxidoreductase (XOR), which catabolizes purines into uric acid and ROS in MFS aortopathy.
METHODS AND RESULTS
In aortic samples from MFS patients, XOR protein expression, revealed by immunohistochemistry, increased in both the tunicae intima and media of the dilated zone. In MFS mice (Fbn1), aortic XOR mRNA transcripts and enzymatic activity of the oxidase form (XO) were augmented in the aorta of 3-month-old mice but not in older animals. The administration of the XOR inhibitor allopurinol (ALO) halted the progression of aortic root aneurysm in MFS mice. ALO administrated before the onset of the aneurysm prevented its subsequent development. ALO also inhibited MFS-associated endothelial dysfunction as well as elastic fiber fragmentation, nuclear translocation of pNRF2 and increased 3'-nitrotyrosine levels, and collagen maturation remodeling, all occurring in the tunica media. ALO reduced the MFS-associated large aortic production of HO, and NOX4 and MMP2 transcriptional overexpression.
CONCLUSIONS
Allopurinol interferes in aortic aneurysm progression acting as a potent antioxidant. This study strengthens the concept that redox stress is an important determinant of aortic aneurysm formation and progression in MFS and warrants the evaluation of ALO therapy in MFS patients.
Topics: Mice; Animals; Marfan Syndrome; Allopurinol; Reactive Oxygen Species; Hydrogen Peroxide; Aortic Aneurysm; Aorta; Disease Models, Animal; Oxidative Stress; Oxidation-Reduction
PubMed: 36347404
DOI: 10.1016/j.freeradbiomed.2022.11.001 -
Seminars in Vascular Surgery Sep 2022Precise preoperative planning for fenestrated and branched endovascular repair of aortic aneurysms is essential for safe and successful surgery. Planning should begin... (Review)
Review
Precise preoperative planning for fenestrated and branched endovascular repair of aortic aneurysms is essential for safe and successful surgery. Planning should begin with a high-quality computed tomography angiography of the chest abdomen and pelvis, which is input into post-processing software to create centerline formatting of the aorta, iliac, and target vessels. The aorta and its branches should then be assessed for aberrant anatomy, dissection, and extent of disease. In any patient with evidence of dissection, a plan should be established for intravascular ultrasound assessment of wire location to confirm the appropriately selected lumen. The proximal and distal seal zones should be selected in areas of a healthy, nonangulated, and parallel vessel free from degeneration calcification and atheroma. The proximal and distal devices can then be selected with 10% to 20% oversizing. Target vessels are evaluated for incorporation and assessed for vessel size, stenosis, dissection, and distance to branching vessels, all of which guide suitability for fenestrated and branched endovascular repair of aortic aneurysms and sizing for bridging stents. The celiac and superior mesenteric arteries should be incorporated for repair, even if evidence of proximal stenosis is identified, as should accessory renal arteries >4 mm. Although total femoral access is now widely used, all access options should be carefully evaluated for size, calcification, and dissection, including bilateral femoral, iliac, subclavian, and brachial vessels. Finally, optimal C-Arm gantry angles should be planned to clearly identify the orifice and first branch of target vessels, as well as proximal and distal sealing zones.
Topics: Aortic Aneurysm; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Constriction, Pathologic; Endovascular Procedures; Humans; Prosthesis Design; Retrospective Studies; Stents; Treatment Outcome
PubMed: 36153066
DOI: 10.1053/j.semvascsurg.2022.07.006 -
Annals of Vascular Surgery Jul 2021Patients unfit for open repair after development a postdissection aortic arch and thoraco-abdominal aneurysm after open ascending aortic replacement for type A...
Patients unfit for open repair after development a postdissection aortic arch and thoraco-abdominal aneurysm after open ascending aortic replacement for type A dissection would have no other treatment options. We report the case of a 75-year-old man with a type A aortic dissection treated by ascending aortic replacement. The patient presented an enlargement of the downstream aorta and thoraco-abdominal aneurysm 6-months after. This patient underwent a three-stage surgical sessions, open surgery for extraanatomical supra-aortic trunks reconstruction, endovascular branched treatment of ascending, arch and descending aorta and another one to perform an endovascular fenestrated reconstruction of thoraco-abdominal and infrarenal aorta.
Topics: Aged; Aortic Dissection; Aorta; Aortic Aneurysm; Aortic Aneurysm, Thoracic; Blood Vessel Prosthesis; Blood Vessel Prosthesis Implantation; Endovascular Procedures; Humans; Male; Stents; Treatment Outcome
PubMed: 33836235
DOI: 10.1016/j.avsg.2021.01.101 -
Inflammation Jun 2022The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation.... (Review)
Review
The role of inflammation in the development of aortic aneurysms is emerging, along with the potential diagnostic and therapeutical potential of this correlation. Abdominal aorta aneurysms have a strong inflammatory substrate since atherosclerosis, which is undoubtedly linked to inflammation, is also a predisposing factor to their formation. Yet, data have emerged that the development of thoracic aorta aneurysms involves several inflammatory pathways, although they were previously referred to as a non-inflammatory disease. Since aortic aneurysms are mainly asymptomatic during their clinical course until their complications-which may be lethal-serum biomarkers for their early diagnosis are a necessity. Studies highlight that inflammation molecules may have a critical role in that direction. In addition, imaging techniques that trace aortic wall inflammation are developed in order to predict aneurysm growth rates and sites vulnerable of rupture. Several anti-inflammatory agents have been also studied in animal models and clinical trials for the treatment of aortic aneurysms. This review highlights the role of inflammation in pathogenesis, diagnosis and treatment of aortic aneurysms.
Topics: Animals; Anti-Inflammatory Agents; Aorta; Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Inflammation
PubMed: 35076833
DOI: 10.1007/s10753-022-01626-z -
European Journal of Cardio-thoracic... Jun 2024The causal association between immune cell traits and aortic aneurysm remains unknown.
OBJECTIVES
The causal association between immune cell traits and aortic aneurysm remains unknown.
METHODS
We performed a bidirectional two-sample Mendelian randomization analysis to explore the causality between 731 immune cell characteristics and the risk of abdominal aortic aneurysm and thoracic aortic aneurysms through publicly available genetic data, respectively. To examine heterogeneity and horizontal pleiotropy, Cochran's Q test and MR-Egger intercept were utilized. Additionally, multivariable Mendelian randomization analysis and meta-analysis were performed in further analysis.
RESULTS
We found that 20 immune phenotypes had a suggestive causality on abdominal aortic aneurysm, and 15 immune phenotypes had a suggestive causal effect on thoracic aortic aneurysm. After further false discovery rate adjustment (q value <0.1), CD20 on IgD+ CD38- B cell (q = 0.053) and CD127 on CD28+ CD4+ T cell (q = 0.096) were associated with an increased risk of abdominal aortic aneurysm, respectively, indicating a significant causality between them. After adjusting for smoking, there is still statistical significance between CD127 on CD28+ CD4+ T cell and abdominal aortic aneurysm. However, after adjusting for lipids, no statistical significance can be observed between CD127 on CD28+ CD4+ T cells and abdominal aortic aneurysm. Furthermore, there is still statistical significance between CD20 on IgD+ CD38- B cells and abdominal aortic aneurysm after adjusting for lipids and smoking, which was further identified by meta-analysis.
CONCLUSIONS
We found a causal association between immune cell traits and aortic aneurysm by genetic methods, thus providing new avenues for future mechanism studies.
Topics: Humans; Mendelian Randomization Analysis; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Risk Factors; Phenotype; Genetic Predisposition to Disease
PubMed: 38833686
DOI: 10.1093/ejcts/ezae229 -
Frontiers in Immunology 2022Aortic disease (aortic aneurysm (AA), dissection (AD)) is a serious threat to patient lives. Little is currently known about the molecular mechanisms and immune...
BACKGROUND
Aortic disease (aortic aneurysm (AA), dissection (AD)) is a serious threat to patient lives. Little is currently known about the molecular mechanisms and immune infiltration patterns underlying the development and progression of thoracic and abdominal aortic aneurysms (TAA and AAA), warranting further research.
METHODS
We downloaded AA (includes TAA and AAA) datasets from the GEO database. The potential biomarkers in TAA and AAA were identified using differential expression analysis and two machine-learning algorithms. The discrimination power of the potential biomarkers and their diagnostic accuracy was assessed in validation datasets using ROC curve analysis. Then, GSEA, KEGG, GO and DO analyses were conducted. Furthermore, two immuno-infiltration analysis algorithms were utilized to analyze the common immune infiltration patterns in TAA and AAA. Finally, a retrospective clinical study was performed on 78 patients with AD, and the serum from 6 patients was used for whole exome sequencing (WES).
RESULTS
The intersection of TAA and AAA datasets yielded 82 differentially expressed genes (DEGs). Subsequently, the biomarkers ( and ) were acquired by screening using two machine-learning algorithms and ROC curve analysis. The functional analysis of DEGs showed significant enrichment in inflammation and regulation of angiogenic pathways. Immune cell infiltration analysis revealed that adaptive and innate immune responses were closely linked to AA progression. However, neither nor was associated with B cell-mediated humoral immunity. expression was correlated with macrophages and with eosinophils. Finally, our retrospective clinical study revealed a hyperinflammatory environment in aortic disease. The WES study identified disease biomarkers and gene variants, some of which may be druggable.
CONCLUSION
The genes and can be used as common biomarkers in TAA and AAA. Large numbers of innate and adaptive immune cells are infiltrated in AA and are closely linked to the development and progression of AA. Moreover, and are highly correlated with the infiltration of immune cells and may be potential targets of immunotherapeutic drugs. Gene mutation research is a promising direction for the treatment of aortic disease.
Topics: Humans; Aortic Aneurysm, Abdominal; Retrospective Studies; Aortic Aneurysm, Thoracic; Biomarkers
PubMed: 36341412
DOI: 10.3389/fimmu.2022.1030976 -
Journal of Molecular and Cellular... Aug 2022Aortic aneurysms, including thoracic aortic aneurysms and abdominal aortic aneurysms, are life-threatening macrovascular diseases with high mortality. The already known... (Review)
Review
Aortic aneurysms, including thoracic aortic aneurysms and abdominal aortic aneurysms, are life-threatening macrovascular diseases with high mortality. The already known key mechanisms implicated in aortic aneurysm pathogenesis involve the remodeling of the extracellular matrix and a set of cellular responses, such as inflammation, oxidative stress and vascular smooth muscle cell dysfunction. Matricellular proteins constitute a group of nonstructural extracellular proteins that link the interaction between cells and their extracellular microenvironment and have been widely reported in different diseases, including aortic aneurysms. In the present review, we summarize the role of various matricellular proteins in the pathogenesis and progression of aortic aneurysms, as well as address the possibility of using these proteins as biomarkers and pathogenic factors, to highlight their clinical significance in aortic aneurysms.
Topics: Aortic Aneurysm; Aortic Aneurysm, Abdominal; Aortic Aneurysm, Thoracic; Biomarkers; Humans; Myocytes, Smooth Muscle
PubMed: 35576729
DOI: 10.1016/j.yjmcc.2022.05.001 -
American Journal of Physiology. Heart... May 2023
Topics: Humans; Aneurysm, Ascending Aorta; Dilatation; Aortic Aneurysm; Phosphoinositide Phospholipase C
PubMed: 36897748
DOI: 10.1152/ajpheart.00687.2022 -
JACC. Cardiovascular Imaging Nov 2019Reconstructive surgery of the aortic valve is being increasingly used in patients with aortic regurgitation and/or aortic aneurysm. Its success depends on restoring... (Review)
Review
Reconstructive surgery of the aortic valve is being increasingly used in patients with aortic regurgitation and/or aortic aneurysm. Its success depends on restoring normal aortic valve and root form. Echocardiography is the most reliable and precise imaging technique because it defines abnormal morphology and function, essential for selecting appropriate substrates and guiding the surgical strategy. Despite technical advances in echocardiography, aortic valve and aortic root morphology and function are still assessed mainly using 2-dimensional echocardiography in clinical practice. This review focuses on the need to use 3-dimensional echocardiography to characterize different forms of aortic valve and root abnormalities and attempts to define echocardiographic predictors of successful valve-root complex repair.
Topics: Aortic Aneurysm; Aortic Valve; Aortic Valve Insufficiency; Cardiac Surgical Procedures; Echocardiography, Three-Dimensional; Hemodynamics; Humans; Predictive Value of Tests; Plastic Surgery Procedures; Recovery of Function; Treatment Outcome
PubMed: 30878428
DOI: 10.1016/j.jcmg.2018.06.032 -
Heart (British Cardiac Society) Sep 2022
Topics: Aortic Aneurysm; Aortitis; Humans
PubMed: 36162847
DOI: 10.1136/heartjnl-2022-321058