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Frontiers in Cardiovascular Medicine 2024Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development,... (Review)
Review
Abdominal Aortic Aneurysm (AAA) is a disease characterized by localized dilation of the abdominal aorta, involving multiple factors in its occurrence and development, ultimately leading to vessel rupture and severe bleeding. AAA has a high mortality rate, and there is a lack of targeted therapeutic drugs. Epigenetic regulation plays a crucial role in AAA, and the treatment of AAA in the epigenetic field may involve a series of related genes and pathways. Abnormal expression of these genes may be a key factor in the occurrence of the disease and could potentially serve as promising therapeutic targets. Understanding the epigenetic regulation of AAA is of significant importance in revealing the mechanisms underlying the disease and identifying new therapeutic targets. This knowledge can contribute to offering AAA patients better clinical treatment options beyond surgery. This review systematically explores various aspects of epigenetic regulation in AAA, including DNA methylation, histone modification, non-coding RNA, and RNA modification. The analysis of the roles of these regulatory mechanisms, along with the identification of relevant genes and pathways associated with AAA, is discussed comprehensively. Additionally, a comprehensive discussion is provided on existing treatment strategies and prospects for epigenetics-based treatments, offering insights for future clinical interventions.
PubMed: 38895538
DOI: 10.3389/fcvm.2024.1394889 -
Frontiers in Cardiovascular Medicine 2024Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to... (Review)
Review
Abdominal aortic aneurysm (AAA) is a significant source of mortality worldwide and carries a mortality of greater than 80% after rupture. Despite extensive efforts to develop pharmacological treatments, there is currently no effective agent to prevent aneurysm growth and rupture. Current treatment paradigms only rely on the identification and surveillance of small aneurysms, prior to ultimate open surgical or endovascular repair. Recently, regenerative therapies have emerged as promising avenues to address the degenerative changes observed in AAA. This review briefly outlines current clinical management principles, characteristics, and pharmaceutical targets of AAA. Subsequently, a thorough discussion of regenerative approaches is provided. These include cellular approaches (vascular smooth muscle cells, endothelial cells, and mesenchymal stem cells) as well as the delivery of therapeutic molecules, gene therapies, and regenerative biomaterials. Lastly, additional barriers and considerations for clinical translation are provided. In conclusion, regenerative approaches hold significant promise for reversal of tissue damages in AAA, necessitating sustained research and innovation to achieve successful and translatable therapies in a new era in AAA management.
PubMed: 38895536
DOI: 10.3389/fcvm.2024.1369785 -
Sensors (Basel, Switzerland) May 2024Over the past two decades, there has been extensive research into surveillance methods for the post-endovascular repair of abdominal aortic aneurysms, highlighting the... (Review)
Review
Over the past two decades, there has been extensive research into surveillance methods for the post-endovascular repair of abdominal aortic aneurysms, highlighting the importance of these technologies in supplementing or even replacing conventional image-screening modalities. This review aims to provide an overview of the current status of alternative surveillance solutions for endovascular aneurysm repair, while also identifying potential aneurysm features that could be used to develop novel monitoring technologies. It offers a comprehensive review of these recent clinical advances, comparing new and standard clinical practices. After introducing the clinical understanding of abdominal aortic aneurysms and exploring current treatment procedures, the paper discusses the current surveillance methods for endovascular repair, contrasting them with recent pressure-sensing technologies. The literature on three commercial pressure-sensing devices for post-endovascular repair surveillance is analyzed. Various pre-clinical and clinical studies assessing the safety and efficacy of these devices are reviewed, providing a comparative summary of their outcomes. The review of the results from pre-clinical and clinical studies suggests a consistent trend of decreased blood pressure in the excluded aneurysm sac post-repair. However, despite successful pressure readings from the aneurysm sac, no strong link has been established to translate these measurements into the presence or absence of endoleaks. Furthermore, the results do not allow for a conclusive determination of ongoing aneurysm sac growth. Consequently, a strong clinical need persists for monitoring endoleaks and aneurysm growth following endovascular repair.
Topics: Aortic Aneurysm, Abdominal; Humans; Endovascular Procedures; Monitoring, Physiologic; Blood Pressure; Pressure; Prostheses and Implants; Endovascular Aneurysm Repair
PubMed: 38894317
DOI: 10.3390/s24113526 -
Journal of Clinical Medicine May 2024The aim of this paper is to propose a sequential deployment technique for the E-nside off-the-shelf endograft that could potentially enhance target visceral vessel...
Partial Deployment to Save Space for Vessel Cannulation When Treating Complex Aortic Aneurysms with Narrow Paravisceral Lumen Is Also Feasible Using Inner-Branched Pre-Cannulated Endografts.
The aim of this paper is to propose a sequential deployment technique for the E-nside off-the-shelf endograft that could potentially enhance target visceral vessel (TVV) cannulation and overstenting in narrow aortic anatomies. All data regarding patients consecutively treated in two aortic centers with the E-nside graft employing the partial deployment technique were included in the study cohort and analyzed. To execute the procedure with partial endograft deployment, the device should be prepared before insertion by advancing, under fluoroscopy, all four dedicated 400 cm long 0.018″ non-hydrophilic guidewires until their proximal ends reach the cranial graft's edge. Anticipating this guidewire placement prevents the inability to do so once the endograft is partially released, avoiding potentially increased friction inside the constricted pre-loaded microchannels. The endograft is then advanced and deployed in the standard fashion, stopping just after the inner branch outlets are fully expanded. Tip capture is released, and the proximal end of the device is opened. Visceral vessel bridging is completed from an upper access in the desired sequence, and the graft is fully released after revascularizing one or more arteries. Preventing the distal edge of the graft from fully expanding improves visceral vessel cannulation and bridging component advancement, especially when dealing with restricted lumina. A total of 26 patients were treated during the period December 2019-March 2024 with the described approach. Procedure was performed in urgent settings in 14/26 cases. The available lumen was narrower than 24 mm at the origin of at least one target vessel in 11 out of 26 cases performed (42.3%). Technical success was obtained in 24 out of 26 cases (92.3%), with failures being due to TVVs loss. No intraoperative death or surgical conversion was recorded, and no early reintervention was needed in the perioperative period. Clinical success at 30 days was therefore 80.7%. The described technique could be considered effective in saving space outside of the graft, allowing for safe navigation and target vessel cannulation in narrow visceral aortas, similar to what has already been reported for outer-branched endografts.
PubMed: 38892771
DOI: 10.3390/jcm13113060 -
International Journal of Molecular... May 2024The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within... (Review)
Review
An Eye into the Aorta: The Role of Extracellular Matrix Regulatory Genes and , from Their Previous Association with Brittle Cornea Syndrome to Their Novel Association with Aortic and Arterial Aneurysmal Diseases.
The extracellular matrix is a complex network of proteins and other molecules that are essential for the support, integrity, and structure of cells and tissues within the human body. The genes and each produce extracellular-matrix-related proteins that, when mutated, have been shown to result in the development of brittle cornea syndrome. This dysfunction results from aberrant protein function resulting in extracellular matrix disruption. Our group recently identified and published the first known associations between variants in these genes and aortic/arterial aneurysms and dissection diseases. This paper delineates the proposed effects of mutated and on various essential extracellular matrix components, including various collagens, TGF-B, clusterin, thrombospondin, and HAPLN-1, and reviews our recent reports associating single-nucleotide variants to these genes' development of aneurysmal and dissection diseases.
Topics: Humans; Transcription Factors; Extracellular Matrix; Joint Instability; Histone-Lysine N-Methyltransferase; Corneal Dystrophies, Hereditary; Ehlers-Danlos Syndrome; Aortic Aneurysm; Mutation; DNA-Binding Proteins; Skin Diseases, Genetic; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Eye Abnormalities; Skin Abnormalities
PubMed: 38892036
DOI: 10.3390/ijms25115848 -
International Journal of Molecular... May 2024Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation...
Human abdominal aortic aneurysms (AAAs) are characterized by increased activity of matrix metalloproteinases (MMP), including MMP-12, alongside macrophage accumulation and elastin degradation, in conjunction with superimposed atherosclerosis. Previous genetic ablation studies have proposed contradictory roles for MMP-12 in AAA development. In this study, we aimed to elucidate if pharmacological inhibition of MMP-12 activity with a phosphinic peptide inhibitor protects from AAA formation and progression in angiotensin (Ang) II-infused Apoe mice. Complimentary studies were conducted in a human ex vivo model of early aneurysm development. Administration of an MMP-12 inhibitor (RXP470.1) protected hypercholesterolemia Apoe mice from Ang II-induced AAA formation and rupture-related death, associated with diminished medial thinning and elastin fragmentation alongside increased collagen deposition. Proteomic analyses confirmed a beneficial effect of MMP-12 inhibition on extracellular matrix remodeling proteins combined with inflammatory pathways. Furthermore, RXP470.1 treatment of mice with pre-existing AAAs exerted beneficial effects as observed through suppressed aortic dilation and rupture, medial thinning, and elastin destruction. Our findings indicate that pharmacological inhibition of MMP-12 activity retards AAA progression and improves survival in mice providing proof-of-concept evidence to motivate translational work for MMP-12 inhibitor therapy in humans.
Topics: Animals; Aortic Aneurysm, Abdominal; Angiotensin II; Matrix Metalloproteinase 12; Mice; Apolipoproteins E; Humans; Matrix Metalloproteinase Inhibitors; Male; Disease Models, Animal; Mice, Knockout; Mice, Inbred C57BL; Elastin; Proteomics
PubMed: 38891996
DOI: 10.3390/ijms25115809 -
Journal of Cardiothoracic Surgery Jun 2024The surgical treatment strategy for aortic arch pathology with a shaggy aorta must be determined on a case-by-case basis because of the risk of catastrophic...
BACKGROUND
The surgical treatment strategy for aortic arch pathology with a shaggy aorta must be determined on a case-by-case basis because of the risk of catastrophic complications, such as brain infarction and spinal cord injury.
CASE PRESENTATION
This report describes the surgical case of two saccular aneurysms of the arch and abdominal aorta associated with a shaggy aorta in a 63-year-old man who underwent total arch replacement and secondary thoracic endovascular aortic repair. Considering the risk of embolization during endovascular therapy, graft replacement for the abdominal aortic aneurysm was initially performed. On postoperative day 28, total arch replacement with the conventional elephant trunk was performed using the functional brain isolation technique, which involves manipulating places far from the atherosclerotic burden, such as arterial inflow for cardiopulmonary bypass and unclamping of neck vessels. On postoperative day 7 after total arch replacement, thoracic endovascular aortic repair was performed across the conventional elephant trunk in the nondiseased descending aorta. No postoperative complications, such as cerebrovascular failure, paraplegia, or embolization to abdominal viscera or lower extremities, occurred. The patient remained asymptomatic.
CONCLUSIONS
The present case suggests that total arch replacement with the conventional elephant trunk and secondary thoracic endovascular aortic repair may be an effective alternative for aortic arch pathology with a shaggy aorta. The strategy for surgical treatment in patients with aortic arch pathologies with a shaggy aorta must be judged on a case-by-case basis, considering patient characteristics, comorbidities, and preoperative evaluation using transesophageal echocardiography and computed tomography angiography, to eliminate potential determinants of intraoperative stroke.
Topics: Humans; Male; Middle Aged; Aorta, Thoracic; Aortic Aneurysm, Thoracic; Endovascular Procedures; Blood Vessel Prosthesis Implantation; Tomography, X-Ray Computed
PubMed: 38890739
DOI: 10.1186/s13019-024-02841-5 -
Journal of the American Heart... Jun 2024Recent studies suggest that immune-mediated inflammation of perivascular adipose tissue of abdominal aortic aneurysms (AAAs) contributes to disease development and...
BACKGROUND
Recent studies suggest that immune-mediated inflammation of perivascular adipose tissue of abdominal aortic aneurysms (AAAs) contributes to disease development and progression. Whether the perivascular adipose tissue of AAA is characterized by a specific adaptive immune signature remains unknown.
METHODS AND RESULTS
To investigate this hypothesis, we sequenced the T-cell receptor β-chain in the perivascular adipose tissue of patients with AAA and compared it with patients with aortic occlusive disease, who share the former anatomical site of the lesion and risk factors but differ in pathogenic mechanisms. Our results demonstrate that patients with AAA have a lower repertoire diversity than those with aortic occlusive disease and significant differences in variable/joining gene segment usage. Furthermore, we identified a set of 7 public T-cell receptor β-chain clonotypes that distinguished AAA and aortic occlusive disease with very high accuracy. We also found that the T-cell receptor β-chain repertoire differentially characterizes small and large AAAs (aortic diameter<55 mm and ≥55 mm, respectively).
CONCLUSIONS
This work supports the hypothesis that T cell-mediated immunity is fundamental in AAA pathogenesis and opens up new clinical perspectives.
Topics: Humans; Aortic Aneurysm, Abdominal; Male; Aged; Female; T-Lymphocytes; Adipose Tissue; Receptors, Antigen, T-Cell, alpha-beta; Middle Aged; Aorta, Abdominal
PubMed: 38888318
DOI: 10.1161/JAHA.123.034096 -
Vascular Specialist International Jun 2024
PubMed: 38887877
DOI: 10.5758/vsi.230075.e -
Cureus May 2024A Type IV endoleak is a very rare complication following endovascular aneurysm repair (EVAR) and differential diagnosis can be difficult. Reported here is a case that...
A Type IV endoleak is a very rare complication following endovascular aneurysm repair (EVAR) and differential diagnosis can be difficult. Reported here is a case that showed the development of a Type IV endoleak after an EVAR procedure, for which a novel software was useful to differentiate that from Type I based on visual confirmation. The 89-year-old man was diagnosed with a large abdominal aortic aneurysm, sized 70 mm, as shown by computed tomography (CT). EVAR was performed in a routine fashion using an Endurant II stent graft. Postoperative CT revealed a massive endoleak around the neck that was difficult to differentiate between Types I and IV. The use of the novel software Viewtify (SCIEMENT, Inc., Tokyo, Japan) to visualize the endoleak with surrounding tissues as real-time three-dimensional computer graphics (3DCG) resulted in confirmation that the endoleak was not from the proximal end but rather the stent graft body. CT findings obtained one week later showed that the endoleak had diminished and no additional procedures were needed. Following a diagnosis of endoleak after EVAR, images viewed with Viewtify helped to confirm the appropriate diagnosis. This novel software was found useful to clarify the position and mechanism of a Type IV endoleak.
PubMed: 38887348
DOI: 10.7759/cureus.60527