scholarly journals Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mingqi Ouyang ◽  
Mi Wang ◽  
Bilian Yu
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Fate ◽  
Mitochondrial Dynamics ◽  
Oxygen Species ◽  
Abdominal Aortic ◽  
Mitochondrial Functions ◽  
Important Player ◽  
Underlying Mechanisms ◽  
Species Production

Abdominal aortic aneurysm (AAA) is defined as a progressive segmental dilation of the abdominal aorta and is associated with high mortality. The characterized features of AAA indicate several underlying mechanisms of AAA formation and progression, including reactive oxygen species production, inflammation, and atherosclerosis. Mitochondrial functions are critical for determining cell fate, and mitochondrial dynamics, especially selective mitochondrial autophagy, which is termed as mitophagy, has emerged as an important player in the pathogenesis of several cardiovascular diseases. The PARKIN/PARIS/PGC1α pathway is associated with AAA formation and has been proposed to play a role in mitochondrial dynamics mediated by the PINK/PARKIN pathway in the pathogenesis underlying AAA. This review is aimed at deepening our understanding of AAA formation and progression, which is vital for the development of potential medical therapies for AAA.

Abstract 311: The Long Non-Coding RNA H19 Regulates Experimental Abdominal Aortic Aneurysm Development and Progression

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Yuhuang Li ◽  
Hong Jin ◽  
Albert Busch ◽  
Ekaterina Chernogubova ◽  
Alexandra Bäcklund ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cell Fate ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cell Fate Decisions ◽  
Knock Down ◽  
Abdominal Aortic ◽  
Aneurysm Development

Background: Long noncoding RNAs (lncRNAs) have emerged as critical epigenetic regulators in various biological processes and diseases. Here we sought to identify and functionally characterize the lncRNA H19 as a novel regulator in abdominal aortic aneurysm development. Methods and Results: We profiled RNA transcript expression in two murine abdominal aortic aneurysm models, Angiotensin II (ANGII) infusion in ApoE-/- mice and porcine pancreatic elastase (PPE) instillation in C57BL/6 wildtype mice. The lncRNA H19 was identified as one of the most highly up-regulated transcripts in both mouse aneurysm models compared to sham-operated controls. This was confirmed by qRT-PCR and in situ hybridization. Experimental knock-down of H19, utilizing site-specific antisense oligonucleotides (LNA-GapmeRs) in vivo , significantly limited aneurysm growth in both models. Upregulated H19 correlated well with smooth muscle cell (SMC) content and its apoptosis in progressing aneurysms. Of importance, a similar pattern could be observed in human AAA tissue samples, and in a novel preclinical LDLR-/- Yucatan mini-pig aneurysm model. In vitro knock-down of H19 markedly decreased apoptotic rates of cultured human aortic SMCs, while overexpression of H19 had the opposite effect. Interestingly, H19-dependent cell fate decisions in SMCs appeared independent of miR-675, which is embedded in the first exon of the H19 gene. A customized transcription factor array and proteomic analysis revealed the hypoxia-inducible factor 1-alpha (HIF1A) and interleukin 1 receptor-like 2 (IL1RL2) as the main downstream effectors being regulated via H19. Conclusion: The lncRNA H19 is a novel regulator of SMC survival and aortic inflammation in AAA development and progression. Ultimately inhibition of H19 expression might serve as a novel molecular therapeutic target for aneurysm disease. Key words: Long noncoding RNAs (lncRNAs); abdominal aortic aneurysm; smooth muscle cells (SMCs); Inflammation

Depletion of CD11c+ cell attenuates progression of abdominal aortic aneurysm

2020 ◽  
Vol 134 (1) ◽  
pp. 33-37
Author(s):  
Keisuke Okuno ◽  
Stephanie Cicalese ◽  
Satoru Eguchi
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Arterial Wall ◽  
Inflammatory Cells ◽  
Matrix Remodeling ◽  
Lower Plasma ◽  
Elastase Activity ◽  
Abdominal Aortic ◽  
Underlying Mechanisms ◽  
Therapeutic Research

Abstract Chronic inflammation of the arterial wall has been implicated in the development of abdominal aortic aneurysm (AAA). However, the detailed molecular mechanism(s) by which inflammatory cells contributes to AAA pathogenesis remains largely unclear. In their article in Clinical Science, Krishna et al. have reported that depletion of CD11c+ dendritic cells inhibited experimental AAA formation in mice. The authors also demonstrated a decrease in CD4 and CD8 positive T cells in the circulation, lower plasma neutrophil elastase activity, and aortic matrix remodeling. These novel findings will help clarify the underlying mechanisms of AAA progression and may provide a new target for future therapeutic research in AAA formation.

scholarly journals Autoimmunity in the Abdominal Aortic Aneurysm and its Association with Smoking

Aorta ◽  
2017 ◽  
Vol 05 (06) ◽  
pp. 159-167
Author(s):  
M. David Tilson
Keyword(s):  
Nitric Oxide ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Cigarette Smoke ◽  
Immune Reaction ◽  
Large Family ◽  
Abdominal Aortic ◽  
Underlying Mechanisms ◽  
Related Proteins

AbstractSmoking increases the risk of abdominal aortic aneurysm (AAA) in both humans and mice, although the underlying mechanisms are not completely understood. An adventitial aortic antigen, AAAP-40, has been partially sequenced. It has motifs with similarities to all three fibrinogen chains and appears to be connected in evolution to a large family of proteins called fibrinogen-related proteins. Fibrinogen may undergo non-enzymatic nitration, which may result from exposure to nitric oxide in cigarette smoke. Nitration of proteins renders them more immunogenic. It has recently been reported that anti-fibrinogen antibody promotes AAA development in mice. Also, anti-fibrinogen antibodies are present in patients with AAA. These matters are reviewed in the overall context of autoimmunity in AAA. The evidence suggests that smoking amplifies an auto-immune reaction that is critical to the pathogenesis of AAA.

scholarly journals Allosteric Activation of PP2A Inhibits Experimental Abdominal Aortic Aneurysm

2021 ◽  
Author(s):  
Xianming Zhou ◽  
Chao Zhang ◽  
Fei Xie ◽  
Wei Wei ◽  
Rui Li ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Murine Model ◽  
Molecular Mechanisms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Phosphatase 2A ◽  
Novel Strategy ◽  
Species Production

Although extremely important, the molecular mechanisms that govern aortic aneurysm (AA) formation and progression are still poorly understood. This deficit represents a critical roadblock toward the development of effective pharmaceutical therapies for the treatment of AA. While dysregulation of Protein Phosphatase 2A (PP2A) is thought to play a role in cardiovascular disease, its role in aortic aneurysm is unknown. The objective of this study is to test the hypothesis that PP2A regulates abdominal aortic aneurysm (AAA) progression in a murine model. In an angiotensin II-induced AAA murine model, the PP2A inhibitor, LB-100, markedly accelerated AAA progression as demonstrated by increased abdominal aortic dilation and mortality. AAA progression was associated with elevated inflammation and extracellular matrix fragmentation, concomitant with increases in both metalloproteinase activity and reactive oxygen species production. Conversely, administration of a novel class of small molecule activators of PP2A (SMAPs) resulted in an antithetical effect. SMAPs effectively reduced AAA incidence along with the corresponding pathologies that were increased with LB-100 treatment. Mechanistically, modulation of PP2A activities in vivo functioned in part via alteration of the ERK1/2 and NFkB signaling pathways, known regulators of AAA progression. These studies, for the first time, demonstrate a role of PP2A in AAA etiology and demonstrate that PP2A activation may represent a novel strategy for the treatment of abdominal aortic aneurysms.

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm

2014 ◽  
Vol 112 (07) ◽  
pp. 87-95 ◽  
Author(s):  
Julio Madrigal-Matute ◽  
Luis M. Blanco-Colio ◽  
Margarita Esteban-Salan ◽  
Monica Torres-Fonseca ◽  
Thibault Lefebvre ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Confidence Interval ◽  
Haemoglobin Concentration ◽  
Aortic Diameter ◽  
Abdominal Aortic ◽  
Tissue Iron ◽  
Circulating Markers ◽  
Iron Retention ◽  
Underlying Mechanisms

SummaryIron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3–5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

Current evidence and prospects for medical treatment of abdominal aortic aneurysms

VASA ◽  
2005 ◽  
Vol 34 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Diehm ◽  
Schmidli ◽  
Dai-Do ◽  
Baumgartner
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Medical Treatment ◽  
Endovascular Treatment ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Significant Morbidity ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal aortic aneurysm (AAA) is a potentially fatal condition with risk of rupture increasing as maximum AAA diameter increases. It is agreed upon that open surgical or endovascular treatment is indicated if maximum AAA diameter exceeds 5 to 5.5cm. Continuing aneurysmal degeneration of aortoiliac arteries accounts for significant morbidity, especially in patients undergoing endovascular AAA repair. Purpose of this review is to give an overview of the current evidence of medical treatment of AAA and describe prospects of potential pharmacological approaches towards prevention of aneurysmal degeneration of small AAAs and to highlight possible adjunctive medical treatment approaches after open surgical or endovascular AAA therapy.

Influence of preoperative statins and aspirin administration on biological and magnetic resonance imaging properties in patients with abdominal aortic aneurysm

VASA ◽  
2020 ◽  
pp. 1-9
Author(s):  
Milos Sladojevic ◽  
Petar Zlatanovic ◽  
Zeljka Stanojevic ◽  
Igor Koncar ◽  
Sasenka Vidicevic ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Abdominal Aortic Aneurysm ◽  
Magnetic Resonance ◽  
Aortic Aneurysm ◽  
Signal Intensity ◽  
Psoas Muscle ◽  
Resonance Imaging ◽  
Maximal Diameter ◽  
Aneurysm Wall ◽  
Abdominal Aortic

Summary: Background: Main objective of this study was to evaluate the influence of statins and/or acetylsalicylic acid on biochemical characteristics of abdominal aortic aneurysm (AAA) wall and intraluminal thrombus (ILT). Patients and methods: Fifty patients with asymptomatic infrarenal AAA were analyzed using magnetic resonance imaging on T1w sequence. Relative ILT signal intensity (SI) was determined as a ratio between ILT and psoas muscle SI. Samples containing the full ILT thickness and aneurysm wall were harvested from the anterior surface at the level of the maximal diameter. The concentration of enzymes such as matrix metalloproteinase (MMP) 9, MMP2 and neutrophil elastase (NE/ELA) were analyzed in ILT and AAA wall; while collagen type III, elastin and proteoglycan 4 were analyzed in harvested AAA wall. Oxidative stress in the AAA wall was assessed by catalase and malondialdehyde activity in tissue samples. Results: Relative ILT signal intensity (1.09 ± 0.41 vs 0.89 ± 0.21, p = 0.013) were higher in non-statin than in statin group. Patients who were taking aspirin had lower relative ILT area (0.89 ± 0.19 vs 1.13. ± 0.44, p = 0.016), and lower relative ILT signal intensity (0.85 [0.73–1.07] vs 1.01 [0.84–1.19], p = 0.021) compared to non-aspirin group. There were higher concentrations of elastin in AAA wall among patients taking both of aspirin and statins (1.21 [0.77–3.02] vs 0.78 (0.49–1.05) ng/ml, p = 0.044) than in patients who did not take both of these drugs. Conclusions: Relative ILT SI was lower in patients taking statin and aspirin. Combination of antiplatelet therapy and statins was associated with higher elastin concentrations in AAA wall.

Associations of coronary and peripheral artery disease with presence, expansion, and rupture of abdominal aortic aneurysm – a grin without a cat!

VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 151-158 ◽  
Author(s):  
Hisato Takagi ◽  
Takuya Umemoto
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Peripheral Artery Disease ◽  
Literature Search ◽  
Systematic Literature Search ◽  
Peripheral Artery ◽  
Epidemiological Evidence ◽  
Abdominal Aortic ◽  
Artery Disease ◽  
Meta Analyses

Abstract. Both coronary and peripheral artery disease are representative atherosclerotic diseases, which are also known to be positively associated with presence of abdominal aortic aneurysm. It is still controversial, however, whether coronary and peripheral artery disease are positively associated with expansion and rupture as well as presence of abdominal aortic aneurysm. In the present article, we overviewed epidemiological evidence, i. e. meta-analyses, regarding the associations of coronary and peripheral artery disease with presence, expansion, and rupture of abdominal aortic aneurysm through a systematic literature search. Our exhaustive search identified seven meta-analyses, which suggest that both coronary and peripheral artery disease are positively associated with presence of abdominal aortic aneurysm, may be negatively associated with expansion of abdominal aortic aneurysm, and might be unassociated with rupture of abdominal aortic aneurysm.

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