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Molecular Research On Abdominal Aortic Aneurysm
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Molecular Research On Abdominal Aortic Aneurysm

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (30 June 2021) | Viewed by 28858

Special Issue Editor

Dr. Dai Yamanouchi

E-Mail Website
Guest Editor
Division of Vascular Surgery, Department of Surgery, University of Wisconsin School of Medicine and Public Health, 1111 Highland Avenue, Madison, WI 53705, USA
Interests: aneurysm; vascular biology; angiogenesis; intimal hyperplasia; macrophage; osteoclastogenesis; MMPs
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Abdominal aortic aneurysm (AAA) is among the 20 leading causes of death in the United States. Currently, open surgical repair and endovascular placement of a stent graft are the mainstay of treatments for AAA, and there are no FDA-approved medical therapies for AAA. Due to an aging patient demographic with known co-morbidities including coronary artery disease, peripheral artery disease, obstructive lung disease, etc., the need exists for non-surgical therapeutic strategies to treat AAA. The risk factors for the development of AAA include age, male gender, family history, cardiovascular disease, and cigarette smoking. The underlying factors causing vessel damage and aneurysmal dilation remain largely unresolved at the cellular and molecular levels, particularly as it relates to understanding temporal differences during aneurysm initiation, progression, and rupture. The topics of this Special Issue include but are not limited to the cell types, factors, and signaling pathways that contribute to aneurysmal disease that could lead to future therapeutic and preventative strategies.

Dr. Dai Yamanouchi
Guest Editor

Manuscript Submission Information

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Keywords

  • abdominal aortic aneurysm (AAA)
  • macrophage
  • smooth muscle cell (SMC)
  • fibroblast
  • endothelial cell
  • protease
  • matrix metalloproteinase (MMP)
  • smoking

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Published Papers (7 papers)

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Editorial

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4 pages, 179 KiB  
Editorial
Unpacking the Complexities of a Silent Killer
by Dai Yamanouchi
Int. J. Mol. Sci. 2023, 24(8), 7125; https://doi.org/10.3390/ijms24087125 - 12 Apr 2023
Viewed by 1102
Abstract
An abdominal aortic aneurysm (AAA) is a life-threatening condition that affects millions of people worldwide [...] Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)

Research

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12 pages, 2160 KiB  
Article
Efficient Suppression of Abdominal Aortic Aneurysm Expansion in Rats through Systemic Administration of Statin-Loaded Nanomedicine
by Natsumi Fukuhara, Yuto Honda, Nao Ukita, Makoto Matsui, Yutaka Miura and Katsuyuki Hoshina
Int. J. Mol. Sci. 2020, 21(22), 8702; https://doi.org/10.3390/ijms21228702 - 18 Nov 2020
Cited by 12 | Viewed by 2618
Abstract
Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and [...] Read more.
Abdominal aortic aneurysm (AAA) is a life-threatening disease. However, no systemically injectable drug has been approved for AAA treatment due to low bioavailability. Polymeric micelles are nanomedicines that have the potential to improve therapeutic efficacy by selectively delivering drugs into disease sites, and research has mainly focused on cancer treatments. Here, we developed a statin-loaded polymeric micelle to treat AAAs in rat models. The micelle showed medicinal efficacy by preventing aortic aneurysm expansion in a dose-dependent manner. Furthermore, the micelle-injected group showed decreased macrophage infiltration and decreased matrix metalloproteinase-9 activity in cases of AAA. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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14 pages, 3685 KiB  
Article
A Novel Hybrid Drug Delivery System for Treatment of Aortic Aneurysms
by Koichi Yoshimura, Hiroki Aoki, Chie Teruyama, Masumi Iijima, Hiromori Tsutsumi, Shun’ichi Kuroda and Kimikazu Hamano
Int. J. Mol. Sci. 2020, 21(15), 5538; https://doi.org/10.3390/ijms21155538 - 2 Aug 2020
Cited by 16 | Viewed by 3528
Abstract
Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug [...] Read more.
Ongoing aortic wall degeneration and subsequent aneurysm exclusion failure are major concerns after an endovascular aneurysm repair with a stent-graft. An ideal solution would be a drug therapy that targets the aortic wall and inhibits wall degeneration. Here, we described a novel drug delivery system, which allowed repetitively charging a graft with therapeutic drugs and releasing them to the aortic wall in vivo. The system was composed of a targeted graft, which was labeled with a small target molecule, and the target-recognizing nanocarrier, which contained suitable drugs. We developed the targeted graft by decorating a biotinylated polyester graft with neutravidin. We created the target-recognizing nanocarrier by conjugating drug-containing liposomes with biotinylated bio-nanocapsules. We successfully demonstrated that the target-recognizing nanocarriers could bind to the targeted graft, both in vitro and in blood vessels of live mice. Moreover, the drug released from our drug delivery system reduced the expression of matrix metalloproteinase-9 in mouse aortas. Thus, this hybrid system represents a first step toward an adjuvant therapy that might improve the long-term outcome of endovascular aneurysm repair. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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21 pages, 2391 KiB  
Article
Identification of Novel microRNA Profiles Dysregulated in Plasma and Tissue of Abdominal Aortic Aneurysm Patients
by Emma Plana, Laura Gálvez, Pilar Medina, Silvia Navarro, Victoria Fornés-Ferrer, Joaquín Panadero and Manuel Miralles
Int. J. Mol. Sci. 2020, 21(13), 4600; https://doi.org/10.3390/ijms21134600 - 28 Jun 2020
Cited by 22 | Viewed by 3253
Abstract
microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma [...] Read more.
microRNAs (miRNAs) are small RNAs that regulate different biological processes. Our objective was to identify miRNAs dysregulated in plasma and tissue of patients with abdominal aortic aneurysm (AAA) and explore new potential targets involved in AAA. Fifty-seven subjects were recruited for a plasma study (30 AAA patients, 16 healthy volunteers and 11 patients with atherosclerosis). The expression level of 179 miRNAs was screened in plasma from a subset of samples, and dysregulated miRNAs were validated in the entire study population. Dysregulated miRNAs were also quantified in aortic tissue of 21 AAA patients and 8 organ donors. Applying a gene set enrichment analysis, an interaction map of dysregulated miRNAs and their targets was built, and selected targets were quantified in tissue samples. miR-27b-3p and miR-221-3p were overexpressed in plasma of AAA patients compared with healthy controls, 1.6 times and 1.9 times, respectively. In AAA tissue, six miRNAs (miR-1, miR-27b-3p, miR-29b-3p, miR-133a-3p, miR-133b, and miR-195-5p) were underexpressed from 1.6 to 4.8 times and four miRNAs (miR-146a-5p, miR-21-5p, miR-144-3p, and miR-103a-3p) were overexpressed from 1.3 to 7.2 times. Thrombospondin-2, a target of miR-195-5p, was increased in AAA tissue and negatively correlated with the expression of miR-195-5p, suggesting their involvement in a common regulatory mechanism. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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16 pages, 2927 KiB  
Article
Therapeutic Effect of Rapamycin on Aortic Dissection in Mice
by Makiko Hayashi-Hori, Hiroki Aoki, Miho Matsukuma, Ryohei Majima, Yohei Hashimoto, Sohei Ito, Saki Hirakata, Norifumi Nishida, Aya Furusho, Satoko Ohno-Urabe and Yoshihiro Fukumoto
Int. J. Mol. Sci. 2020, 21(9), 3341; https://doi.org/10.3390/ijms21093341 - 8 May 2020
Cited by 15 | Viewed by 3985
Abstract
Aortic dissection (AD) is a serious clinical condition that is unpredictable and frequently results in fatal outcome. Although rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has been reported to be effective in preventing aortopathies in mouse models, its mode of action [...] Read more.
Aortic dissection (AD) is a serious clinical condition that is unpredictable and frequently results in fatal outcome. Although rapamycin, an inhibitor of mechanistic target of rapamycin (mTOR), has been reported to be effective in preventing aortopathies in mouse models, its mode of action has yet to be clarified. A mouse AD model that was created by the simultaneous administration of β-aminopropionitrile (BAPN) and angiotensin II (AngII) for 14 days. Rapamycin treatment was started either at day 1 or at day 7 of BAPN+AngII challenge, and continued throughout the observational period. Rapamycin was effective both in preventing AD development and in suppressing AD progression. On the other hand, gefitinib, an inhibitor of growth factor signaling, did not show such a beneficial effect, even though both rapamycin and gefitinib suppressed cell cycle activation in AD. Rapamycin suppressed cell cycle-related genes and induced muscle development-related genes in an AD-related gene expression network without a major impact on inflammation-related genes. Rapamycin augmented the activation of Akt1, Akt2, and Stat3, and maintained the contractile phenotype of aortic smooth muscle cells. These findings indicate that rapamycin was effective both in preventing the development and in suppressing the progression of AD, indicating the importance of the mTOR pathway in AD pathogenesis. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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Review

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17 pages, 1428 KiB  
Review
Risk Factors and Mouse Models of Abdominal Aortic Aneurysm Rupture
by Smriti Murali Krishna, Susan K. Morton, Jiaze Li and Jonathan Golledge
Int. J. Mol. Sci. 2020, 21(19), 7250; https://doi.org/10.3390/ijms21197250 - 30 Sep 2020
Cited by 26 | Viewed by 4886
Abstract
Abdominal aortic aneurysm (AAA) rupture is an important cause of death in older adults. In clinical practice, the most established predictor of AAA rupture is maximum AAA diameter. Aortic diameter is commonly used to assess AAA severity in mouse models studies. AAA rupture [...] Read more.
Abdominal aortic aneurysm (AAA) rupture is an important cause of death in older adults. In clinical practice, the most established predictor of AAA rupture is maximum AAA diameter. Aortic diameter is commonly used to assess AAA severity in mouse models studies. AAA rupture occurs when the stress (force per unit area) on the aneurysm wall exceeds wall strength. Previous research suggests that aortic wall structure and strength, biomechanical forces on the aorta and cellular and proteolytic composition of the AAA wall influence the risk of AAA rupture. Mouse models offer an opportunity to study the association of these factors with AAA rupture in a way not currently possible in patients. Such studies could provide data to support the use of novel surrogate markers of AAA rupture in patients. In this review, the currently available mouse models of AAA and their relevance to the study of AAA rupture are discussed. The review highlights the limitations of mouse models and suggests novel approaches that could be incorporated in future experimental AAA studies to generate clinically relevant results. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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33 pages, 1653 KiB  
Review
Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm
by Rijan Gurung, Andrew Mark Choong, Chin Cheng Woo, Roger Foo and Vitaly Sorokin
Int. J. Mol. Sci. 2020, 21(17), 6334; https://doi.org/10.3390/ijms21176334 - 31 Aug 2020
Cited by 82 | Viewed by 8740
Abstract
Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and [...] Read more.
Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology. Full article
(This article belongs to the Special Issue Molecular Research On Abdominal Aortic Aneurysm)
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