Submit to Biomedicines Review for Biomedicines Propose a Special Issue

Journal Browser

Aortic Aneurysms: Vascular Remodeling and Repair

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 30497

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special issue Aortic Aneurysms: Vascular Remodeling and Repair book cover image

Share This Special Issue

Special Issue Editor

Dr. Elena Kaschina

E-Mail Website
Guest Editor

Center for Cardiovascular Research and Institute of Pharmacology, Charité – Universitätsmedizin Berlin, Hessische Strasse 3-4, D-10115 Berlin, Germany
Interests: vascular remodelling; Renin-Angiotensin-Aldosterone system; extracellular matrix; proteolysis; matrix metalloproteinases; aneurysm
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Aortic aneurysm is a multifactorial disease that is characterized by vascular remodeling due to degradation of the extracellular matrix and reduced vascular repair. It is commonly associated with atherosclerosis, hypertension, and thrombotic disorders. Our understanding of the pathogenesis of aneurysm has significantly increased over the last few decades, with data pointing to the roles of genetics, hemodynamics, inflammation, and immune response. Nevertheless, no pharmacotherapy is available to date. Present treatment options are restricted to surgical interventions such as endovascular stents or open surgical procedures that are not appropriate for all patients. Thus, there is a need for specific and effective new treatments that prevent aneurysmal growth, reduce the risk of rupture, and prevent aneurysmal extension after surgical repair. New discoveries in the field of translational biology, cell therapy, and regenerative medicine, together with new approaches to experimental design and target drug release, should accelerate the development of new therapies.

This Special Issue invites both original manuscripts that describe novel findings and cutting-edge review articles that illustrate recent advances in molecular and cell biology, pathophysiology, biomarkers, novel non-surgical medications, and targeted drug delivery for aortic aneurysm.

Dr. Elena Kaschina
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

aortic aneurysm
pathogenesis
pharmacological therapy
experimental model
drug delivery

Published Papers (11 papers)

Download All Papers

Editorial

Jump to: Research, Review

3 pages, 184 KiB

Open AccessEditorial

Aortic Aneurysm: Finding the Right Target

by Elena Kaschina

Biomedicines 2023, 11(5), 1345; https://doi.org/10.3390/biomedicines11051345 - 03 May 2023

Viewed by 882

Abstract

This Special Issue of Biomedicines highlights many important scientific findings in aneurysm research [...] Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

Research

Jump to: Editorial, Review

14 pages, 3431 KiB

Open AccessArticle

The Ratio of the Size of the Abdominal Aortic Aneurysm to That of the Unchanged Aorta as a Risk Factor for Its Rupture

by Maciej Jusko, Piotr Kasprzak, Alicja Majos and Waclaw Kuczmik

Biomedicines 2022, 10(8), 1997; https://doi.org/10.3390/biomedicines10081997 - 17 Aug 2022

Cited by 3 | Viewed by 1326

Abstract

Background: A ruptured abdominal aortic aneurysm is a severe condition associated with high mortality. Currently, the most important criterion used to estimate the risk of its rupture is the size of the aneurysm, but due to patients’ anatomical variability, many aneurysms have a high risk of rupture with a small aneurysm size. We asked ourselves whether individual differences in anatomy could be taken into account when assessing the risk of rupture. Methods: Based on the CT scan image, aneurysm and normal aorta diameters were collected from 186 individuals and compared in patients with ruptured and unruptured aneurysms. To take into account anatomical differences between patients, diameter ratios were calculated by dividing the aneurysm diameter by the diameter of the normal aorta at various heights, and then further comparisons were made. Results: It was found that the calculated ratios differ between patients with ruptured and unruptured aneurysms. This observation is also present in patients with small aneurysms, with its maximal size below the level that indicates the need for surgical treatment. For small aneurysms, the ratios help us to estimate the risk of rupture better than the maximum sac size (AUC: 0.783 vs. 0.650). Conclusions: The calculated ratios appear to be a valuable feature to indicate which of the small aneurysms have a high risk of rupture. The obtained results suggest the need for further confirmation of their usefulness in subsequent groups of patients. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

13 pages, 20296 KiB

Open AccessArticle

Identification of the Key Genes and Potential Therapeutic Compounds for Abdominal Aortic Aneurysm Based on a Weighted Correlation Network Analysis

by Lin Li, Kejia Kan, Prama Pallavi and Michael Keese

Biomedicines 2022, 10(5), 1052; https://doi.org/10.3390/biomedicines10051052 - 02 May 2022

Cited by 3 | Viewed by 1974

Abstract

Background: There is still an unmet need for therapeutic drugs for patients with an abdominal aortic aneurysm (AAA), especially for candidates unsuitable for surgical or interventional repair. Therefore, the purpose of this in silico study is to identify significant genes and regulatory mechanisms in AAA patients to predicate the potential therapeutic compounds for significant genes. Methods: The GSE57691 dataset was obtained from Gene Expression Omnibus (GEO) and used to identify the differentially expressed genes (DEGs) and weighted correlation network analysis (WGCNA). The biological function of DEGs was determined using gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). AAA-related genes were obtained from the Comparative Toxicogenomics Database (CTD) using the keywords: aortic aneurysm and abdominal. The hub genes in AAA were obtained by overlapping DEGs, WGCNA-based hub genes, and CTD-based genes. The diagnostic values of hub genes were determined using ROC curve analysis. Hereby, a TF-miRNA-hub gene network was constructed based on the miRnet database. Using these data, potential therapeutic compounds for the therapy of AAA were predicted based on the Drug Gene Interaction Database (DGIdb). Results: A total of 218 DEGs (17 upregulated and 201 downregulated) and their biological function were explored; 4093 AAA-related genes were derived by text mining. Three hub modules and 144 hub genes were identified by WGCNA. asparagine synthetase (ASNS), axin-related protein 2 (AXIN2), melanoma cell adhesion molecule (MCAM), and the testis-specific Y-encoded-like protein 1 (TSPYL1) were obtained as intersecting hub genes and the diagnostic values were confirmed with ROC curves. As potential compounds targeting the hub genes, asparaginase was identified as the target compound for ASNS. Prednisolone and abiraterone were identified as compounds targeting TSPYL1. For MCAM and TSPYL1, no potential therapeutic compound could be predicted. Conclusion: Using WGCNA analysis and text mining, pre-existing gene expression data were used to provide novel insight into potential AAA-related protein targets. For two of these targets, compounds could be predicted. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

21 pages, 5490 KiB

Open AccessArticle

Cycloastragenol Inhibits Experimental Abdominal Aortic Aneurysm Progression

by Leander Gaarde Melin, Julie Husted Dall, Jes S. Lindholt, Lasse B. Steffensen, Hans Christian Beck, Sophie L. Elkrog, Pernille D. Clausen, Lars Melholt Rasmussen and Jane Stubbe

Biomedicines 2022, 10(2), 359; https://doi.org/10.3390/biomedicines10020359 - 02 Feb 2022

Cited by 5 | Viewed by 3120

Abstract

The pathogenesis of abdominal aortic aneurysm involves vascular inflammation and elastin degradation. Astragalusradix contains cycloastragenol, which is known to be anti-inflammatory and to protect against elastin degradation. We hypothesized that cycloastragenol supplementation inhibits abdominal aortic aneurysm progression. Abdominal aortic aneurysm was induced in male rats by intraluminal elastase infusion in the infrarenal aorta and treated daily with cycloastragenol (125 mg/kg/day). Aortic expansion was followed weekly by ultrasound for 28 days. Changes in aneurysmal wall composition were analyzed by mRNA levels, histology, zymography and explorative proteomic analyses. At day 28, mean aneurysm diameter was 37% lower in the cycloastragenol group (p < 0.0001). In aneurysm cross sections, elastin content was insignificantly higher in the cycloastragenol group (10.5% ± 5.9% vs. 19.9% ± 16.8%, p = 0.20), with more preserved elastin lamellae structures (p = 0.0003) and without microcalcifications. Aneurysmal matrix metalloprotease-2 activity was reduced by the treatment (p = 0.022). Messenger RNA levels of inflammatory- and anti-oxidative markers did not differ between groups. Explorative proteomic analysis showed no difference in protein levels when adjusting for multiple testing. Among proteins displaying nominal regulation were fibulin-5 (p = 0.02), aquaporin-1 (p = 0.02) and prostacyclin synthase (p = 0.007). Cycloastragenol inhibits experimental abdominal aortic aneurysm progression. The suggested underlying mechanisms involve decreased matrix metalloprotease-2 activity and preservation of elastin and reduced calcification, thus, cycloastragenol could be considered for trial in abdominal aortic aneurysm patients. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

15 pages, 2428 KiB

Open AccessArticle

A Systematic Review and Meta-Analysis of the Effect of Pentagalloyl Glucose Administration on Aortic Expansion in Animal Models

by Jonathan Golledge, Shivshankar Thanigaimani and James Phie

Biomedicines 2021, 9(10), 1442; https://doi.org/10.3390/biomedicines9101442 - 11 Oct 2021

Cited by 3 | Viewed by 1568

Abstract

Background: The aim of this systematic review was to pool evidence from studies testing if pentagalloyl glucose (PGG) limited aortic expansion in animal models of abdominal aortic aneurysm (AAA). Methods: The review was conducted according to the PRISMA guidelines and registered with PROSPERO. The primary outcome was aortic expansion assessed by direct measurement. Secondary outcomes included aortic expansion measured by ultrasound and aortic diameter at study completion. Sub analyses examined the effect of PGG delivery in specific forms (nanoparticles, periadventitial or intraluminal), and at different times (from the start of AAA induction or when AAA was established), and tested in different animals (pigs, rats and mice) and AAA models (calcium chloride, periadventitial, intraluminal elastase or angiotensin II). Meta-analyses were performed using Mantel-Haenszel’s methods with random effect models and reported as mean difference (MD) and 95% confidence intervals (CIs). Risk of bias was assessed with a customized tool. Results: Eleven studies reported in eight publications involving 214 animals were included. PGG significantly reduced aortic expansion measured by direct observation (MD: −66.35%; 95% CI: −108.44, −24.27; p = 0.002) but not ultrasound (MD: −32.91%; 95% CI: −75.16, 9.33; p = 0.127). PGG delivered intravenously within nanoparticles significantly reduced aortic expansion, measured by both direct observation (MD: −116.41%; 95% CI: −132.20, −100.62; p < 0.001) and ultrasound (MD: −98.40%; 95% CI: −113.99, −82.81; p < 0.001). In studies measuring aortic expansion by direct observation, PGG administered topically to the adventitia of the aorta (MD: −28.41%; 95% CI −46.57, −10.25; p = 0.002), studied in rats (MD: −56.61%; 95% CI: −101.76, −11.46; p = 0.014), within the calcium chloride model (MD: −56.61%; 95% CI: −101.76, −11.46; p = 0.014) and tested in established AAAs (MD: −90.36; 95% CI: −135.82, −44.89; p < 0.001), significantly reduced aortic expansion. The findings of other analyses were not significant. The risk of bias of all studies was high. Conclusion: There is inconsistent low-quality evidence that PGG inhibits aortic expansion in animal models. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

16 pages, 2213 KiB

Open AccessArticle

Use of MALDI Mass Spectrometry Imaging to Identify Proteomic Signatures in Aortic Aneurysms after Endovascular Repair

by Matthias Buerger, Oliver Klein, Sebastian Kapahnke, Verena Mueller, Jan Paul Frese, Safwan Omran, Andreas Greiner, Manuela Sommerfeld, Elena Kaschina, Anett Jannasch, Claudia Dittfeld, Adrian Mahlmann and Irene Hinterseher

Biomedicines 2021, 9(9), 1088; https://doi.org/10.3390/biomedicines9091088 - 26 Aug 2021

Cited by 5 | Viewed by 2569

Abstract

Endovascular repair (EVAR) has become the standard procedure in treating thoracic (TAA) or abdominal aortic aneurysms (AAA). Not entirely free of complications, a persisting perfusion of the aneurysm after EVAR, called Endoleak (EL), leads to reintervention and risk of secondary rupture. How the aortic wall responds to the implantation of a stentgraft and EL is mostly uncertain. We present a pilot study to identify peptide signatures and gain new insights in pathophysiological alterations of the aortic wall after EVAR using matrix-assisted laser desorption or ionization mass spectrometry imaging (MALDI-MSI). In course of or accompanying an open aortic repair, tissue sections from 15 patients (TAA = 5, AAA = 5, EVAR = 5) were collected. Regions of interest (tunica media and tunica adventitia) were defined and univariate (receiver operating characteristic analysis) statistical analysis for subgroup comparison was used. This proof-of-concept study demonstrates that MALDI-MSI is feasible to identify discriminatory peptide signatures separating TAA, AAA and EVAR. Decreased intensity distributions for actin, tropomyosin, and troponin after EVAR suggest impaired contractility in vascular smooth muscle cells. Furthermore, inability to provide energy caused by impaired respiratory chain function and continuous degradation of extracellular matrix components (collagen) might support aortic wall destabilization. In case of EL after EVAR, this mechanism may result in a weakened aortic wall with lacking ability to react on reinstating pulsatile blood flow. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

14 pages, 1604 KiB

Open AccessArticle

Syndecan-1 Expression Is Increased in the Aortic Wall of Patients with Type 2 Diabetes but Is Unrelated to Elevated Fasting Plasma Glucagon-Like Peptide-1

by Stelia Ntika, Linda M. Tracy, Anders Franco-Cereceda, Hanna M. Björck and Camilla Krizhanovskii

Biomedicines 2021, 9(6), 697; https://doi.org/10.3390/biomedicines9060697 - 20 Jun 2021

Cited by 4 | Viewed by 1984

Abstract

A reduced prevalence of a thoracic aortic aneurysm (thoracic AA) is observed in type 2 diabetes (T2D). Glucagon-like peptide-1 (GLP-1)/GLP-1-based anti-diabetic therapy has indicated protective effects in thoracic AA and regulates the processes controlling the vascular tissue expression of Syndecan-1 (Sdc-1). Sdc-1 expression on macrophages infiltrating the aortic tissue contributes to a counter-regulatory response to thoracic AA formation in animal models through the interplay with inflammation/proteolytic activity. We hypothesized that elevated fasting plasma GLP-1 (fpGLP-1) increases the aortic Sdc-1 expression in T2D, which may contribute to a reduced prevalence of thoracic AA. Consequently, we determined whether T2D/thoracic AA associates with an altered Sdc-1 expression in the aortic tissue and the possible associations with fpGLP-1 and inflammation/proteolytic activity. From a cohort of surgical patients with an aortic valve pathology, we compared different disease groups (T2D/thoracic AA) with the same sub-cohort group of controls (patients without T2D and thoracic AA). The MMP-2 activity and Sdc-1, GLP-1R and CD68 expression were analyzed in the aortic tissue. GLP-1, Sdc-1 and cytokines were analyzed in the plasma. The aortic Sdc-1 expression was increased in T2D patients but did not correlate with fpGLP-1. Thoracic AA was associated with an increased aortic expression of Sdc-1 and the macrophage marker CD68. CD68 was not detected in T2D. In conclusion, an increased aortic Sdc-1 expression may contribute to a reduced prevalence of thoracic AA in T2D. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

10 pages, 874 KiB

Open AccessArticle

Intra-Operative Video-Based Measurement of Biaxial Strains of the Ascending Thoracic Aorta

by Shaiv Parikh, Berta Ganizada, Gijs Debeij, Ehsan Natour, Jos Maessen, Bart Spronck, Leon Schurgers, Tammo Delhaas, Wouter Huberts, Elham Bidar and Koen Reesink

Biomedicines 2021, 9(6), 670; https://doi.org/10.3390/biomedicines9060670 - 11 Jun 2021

Cited by 5 | Viewed by 2491

Abstract

Local biaxial deformation measurements are essential for the in-depth investigation of tissue properties and remodeling of the ascending thoracic aorta, particularly in aneurysm formation. Current clinical imaging modalities pose limitations around the resolution and tracking of anatomical markers. We evaluated a new intra-operative video-based method to assess local biaxial strains of the ascending thoracic aorta. In 30 patients undergoing open-chest surgery, we obtained repeated biaxial strain measurements, at low- and high-pressure conditions. Precision was very acceptable, with coefficients of variation for biaxial strains remaining below 20%. With our four-marker arrangement, we were able to detect significant local differences in the longitudinal strain as well as in circumferential strain. Overall, the magnitude of strains we obtained (range: 0.02–0.05) was in line with previous reports using other modalities. The proposed method enables the assessment of local aortic biaxial strains and may enable new, clinically informed mechanistic studies using biomechanical modeling as well as mechanobiological profiling. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

17 pages, 2206 KiB

Open AccessArticle

Weighted Gene Co-Expression Network Analysis Reveals Key Genes and Potential Drugs in Abdominal Aortic Aneurysm

by Ke-Jia Kan, Feng Guo, Lei Zhu, Prama Pallavi, Martin Sigl and Michael Keese

Biomedicines 2021, 9(5), 546; https://doi.org/10.3390/biomedicines9050546 - 13 May 2021

Cited by 7 | Viewed by 3495

Abstract

Abdominal aortic aneurysm (AAA) is a prevalent aortic disease that causes high mortality due to asymptomatic gradual expansion and sudden rupture. The underlying molecular mechanisms and effective pharmaceutical therapy for preventing AAA progression have not been fully identified. In this study, we identified the key modules and hub genes involved in AAA growth from the GSE17901 dataset in the Gene Expression Omnibus (GEO) database through the weighted gene co-expression network analysis (WGCNA). Key genes were further selected and validated in the mouse dataset (GSE12591) and human datasets (GSE7084, GSE47472, and GSE57691). Finally, we predicted drug candidates targeting key genes using the Drug–Gene Interaction database. Overall, we identified key modules enriched in the mitotic cell cycle, GTPase activity, and several metabolic processes. Seven key genes (CCR5, ADCY5, ADCY3, ACACB, LPIN1, ACSL1, UCP3) related to AAA progression were identified. A total of 35 drugs/compounds targeting the key genes were predicted, which may have the potential to prevent AAA progression. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

20 pages, 3150 KiB

Open AccessArticle

Gene Regulatory Network Analysis of Perivascular Adipose Tissue of Abdominal Aortic Aneurysm Identifies Master Regulators of Key Pathogenetic Pathways

by Luca Piacentini, Mattia Chiesa and Gualtiero Ivanoe Colombo

Biomedicines 2020, 8(8), 288; https://doi.org/10.3390/biomedicines8080288 - 14 Aug 2020

Cited by 9 | Viewed by 3152

Abstract

The lack of medical therapy to treat abdominal aortic aneurysm (AAA) stems from our inadequate understanding of the mechanisms underlying AAA pathogenesis. To date, the only available treatment option relies on surgical intervention, which aims to prevent AAA rupture. Identifying specific regulators of pivotal pathogenetic mechanisms would allow the development of novel treatments. With this work, we sought to identify regulatory factors associated with co-expressed genes characterizing the diseased perivascular adipose tissue (PVAT) of AAA patients, which is crucially involved in AAA pathogenesis. We applied a reverse engineering approach to identify cis-regulatory elements of diseased PVAT genes, the associated transcription factors, and upstream regulators. Finally, by analyzing the topological properties of the reconstructed regulatory disease network, we prioritized putative targets for AAA interference treatment options. Overall, we identified NFKB1, SPIB, and TBP as the most relevant transcription factors, as well as MAPK1 and GSKB3 protein kinases and RXRA nuclear receptor as key upstream regulators. We showed that these factors could regulate different co-expressed gene subsets in AAA PVAT, specifically associated with both innate and antigen-driven immune response pathways. Inhibition of these factors may represent a novel option for the development of efficient immunomodulatory strategies to treat AAA. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

35 pages, 649 KiB

Open AccessReview

AAA Revisited: A Comprehensive Review of Risk Factors, Management, and Hallmarks of Pathogenesis

by Veronika Kessler, Johannes Klopf, Wolf Eilenberg, Christoph Neumayer and Christine Brostjan

Biomedicines 2022, 10(1), 94; https://doi.org/10.3390/biomedicines10010094 - 02 Jan 2022

Cited by 33 | Viewed by 6067

Abstract

Despite declining incidence and mortality rates in many countries, the abdominal aortic aneurysm (AAA) continues to represent a life-threatening cardiovascular condition with an overall prevalence of about 2–3% in the industrialized world. While the risk of AAA development is considerably higher for men of advanced age with a history of smoking, screening programs serve to detect the often asymptomatic condition and prevent aortic rupture with an associated death rate of up to 80%. This review summarizes the current knowledge on identified risk factors, the multifactorial process of pathogenesis, as well as the latest advances in medical treatment and surgical repair to provide a perspective for AAA management. Full article

(This article belongs to the Special Issue Aortic Aneurysms: Vascular Remodeling and Repair)

Journal Menu

Journal Browser

Aortic Aneurysms: Vascular Remodeling and Repair

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI