Lipid Levels In Patients With Abdominal Aortic Dilatation And Abdominal Aortic Aneurysm (Aaa)

Abstract Abdominal aortic aneurysm (AAA) is an inflammatory vascular disease characterized by structural deterioration of the aorta caused by inflammation and oxidative stress, leading to aortic dilatation and rupture. Peroxiredoxin 2 (PRDX2), an antioxidant enzyme, has been reported as a potential negative regulator of inflammatory vascular diseases, and it has been identified as a protein that is increased in patients with ruptured AAA compared to patients with nonruptured AAA. In this study, we demonstrated that PRDX2 was a pivotal factor involved in the inhibition of AAA progression. PRDX2 levels were increased in AAA compared with those in normal aortas in both humans and mice. Ultrasound imaging revealed that the loss of PRDX2 accelerated the development of AAA in the early stages and increased AAA incidence in mice infused with angiotensin II (Ang II). Prdx2−/− mice infused with Ang II exhibited increased aortic dilatation and maximal aortic diameter without a change in blood pressure. Structural deterioration of the aortas from Prdx2−/− mice infused with Ang II was associated with increases in the degradation of elastin, oxidative stress, and intramural thrombi caused by microhemorrhages, immature neovessels, and the activation of matrix metalloproteinases compared to that observed in controls. Moreover, an increase in inflammatory responses, including the production of cell adhesion molecules and the accumulation of inflammatory cells and proinflammatory cytokines due to PRDX2 deficiency, accelerated Ang II-induced AAA progression. Our data confirm that PRDX2 plays a role as a negative regulator of the pathological process of AAA and suggest that increasing PRDX2 activity may be a novel strategy for the prevention and treatment of AAA.

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Transcriptional profiling and network analysis of the murine angiotensin II-induced abdominal aortic aneurysm

Physiological Genomics ◽

10.1152/physiolgenomics.00044.2011 ◽

2011 ◽

Vol 43 (17) ◽

pp. 993-1003 ◽

Cited By ~ 42

Author(s):

Joshua M. Spin ◽

Mark Hsu ◽

Junya Azuma ◽

Maureen M. Tedesco ◽

Alicia Deng ◽

...

Keyword(s):

Gene Expression ◽

Abdominal Aortic Aneurysm ◽

Angiotensin Ii ◽

Network Analysis ◽

Aortic Aneurysm ◽

Mapk Signaling ◽

Aortic Dilatation ◽

Ang Ii ◽

Abdominal Aortic ◽

Aneurysm Development

We sought to characterize temporal gene expression changes in the murine angiotensin II (ANG II)-ApoE−/− model of abdominal aortic aneurysm (AAA). Aortic ultrasound measurements were obtained over the 28-day time-course. Harvested suprarenal aortic segments were evaluated with whole genome expression profiling at 7, 14, and 28 days using the Agilent Whole Mouse Genome microarray platform and Statistical Analysis of Microarrays at a false discovery rate of <1%. A group of angiotensin-treated mice experienced contained rupture (CR) within 7 days and were analyzed separately. Progressive aortic dilatation occurred throughout the treatment period. However, the numerous early expression differences between ANG II-treated and control were not sustained over time. Ontologic analysis revealed widespread upregulation of inflammatory, immune, and matrix remodeling genes with ANG II treatment, among other pathways such as apoptosis, cell cycling, angiogenesis, and p53 signaling. CR aneurysms displayed significant decreases in TGF-β/BMP-pathway signaling, MAPK signaling, and ErbB signaling genes vs. non-CR/ANG II-treated samples. We also performed literature-based network analysis, extracting numerous highly interconnected genes associated with aneurysm development such as Spp1, Myd88, Adam17 and Lox. 1) ANG II treatment induces extensive early differential expression changes involving abundant signaling pathways in the suprarenal abdominal aorta, particularly wide-ranging increases in inflammatory genes with aneurysm development. 2) These gene expression changes appear to dissipate with time despite continued growth, suggesting that early changes in gene expression influence disease progression in this AAA model, and that the aortic tissue adapts to prolonged ANG II infusion. 3) Network analysis identified nexus genes that may constitute aneurysm biomarkers or therapeutic targets.

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TGFβ (Transforming Growth Factor-β) Blockade Induces a Human-Like Disease in a Nondissecting Mouse Model of Abdominal Aortic Aneurysm

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.117.309999 ◽

2017 ◽

Vol 37 (11) ◽

pp. 2171-2181 ◽

Cited By ~ 27

Author(s):

Fabien Lareyre ◽

Marc Clément ◽

Juliette Raffort ◽

Stefanie Pohlod ◽

Meghana Patel ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Growth Factor ◽

Aortic Aneurysm ◽

Aortic Wall ◽

Transforming Growth Factor ◽

Transforming Growth Factor Β ◽

Aortic Dilatation ◽

Intraluminal Thrombus ◽

Abdominal Aortic ◽

New Models

Objective— Current experimental models of abdominal aortic aneurysm (AAA) do not accurately reproduce the major features of human AAA. We hypothesized that blockade of TGFβ (transforming growth factor-β) activity—a guardian of vascular integrity and immune homeostasis—would impair vascular healing in models of nondissecting AAA and would lead to sustained aneurysmal growth until rupture. Approach and Results— Here, we test this hypothesis in the elastase-induced AAA model in mice. We analyze AAA development and progression using ultrasound in vivo, synchrotron-based ultrahigh resolution imaging ex vivo, and a combination of biological, histological, and flow cytometry-based cellular and molecular approaches in vitro. Systemic blockade of TGFβ using a monoclonal antibody induces a transition from a self-contained aortic dilatation to a model of sustained aneurysmal growth, associated with the formation of an intraluminal thrombus. AAA growth is associated with wall disruption but no medial dissection and culminates in fatal transmural aortic wall rupture. TGFβ blockade enhances leukocyte infiltration both in the aortic wall and the intraluminal thrombus and aggravates extracellular matrix degradation. Early blockade of IL-1β or monocyte-dependent responses substantially limits AAA severity. However, blockade of IL-1β after disease initiation has no effect on AAA progression to rupture. Conclusions— Endogenous TGFβ activity is required for the healing of AAA. TGFβ blockade may be harnessed to generate new models of AAA with better relevance to the human disease. We expect that the new models will improve our understanding of the pathophysiology of AAA and will be useful in the identification of new therapeutic targets.

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Cell proliferation detected using [18F]FLT PET/CT as an early marker of abdominal aortic aneurysm

Journal of Nuclear Cardiology ◽

10.1007/s12350-019-01946-y ◽

2019 ◽

Cited By ~ 3

Author(s):

Richa Gandhi ◽

Christopher Cawthorne ◽

Lucinda J. L. Craggs ◽

John D. Wright ◽

Juozas Domarkas ◽

...

Keyword(s):

Cell Proliferation ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Saline Control ◽

Aortic Dilatation ◽

Nucleoside Transporter ◽

Flt Pet ◽

Gamma Counting ◽

Abdominal Aortic ◽

Pet Ct

Abstract Background Abdominal aortic aneurysm (AAA) is a focal aortic dilatation progressing towards rupture. Non-invasive AAA-associated cell proliferation biomarkers are not yet established. We investigated the feasibility of the cell proliferation radiotracer, fluorine-18-fluorothymidine ([18F]FLT) with positron emission tomography/computed tomography (PET/CT) in a progressive pre-clinical AAA model (angiotensin II, AngII infusion). Methods and Results Fourteen-week-old apolipoprotein E-knockout (ApoE−/−) mice received saline or AngII via osmotic mini-pumps for 14 (n = 7 and 5, respectively) or 28 (n = 3 and 4, respectively) days and underwent 90-minute dynamic [18F]FLT PET/CT. Organs were harvested from independent cohorts for gamma counting, ultrasound scanning, and western blotting. [18F]FLT uptake was significantly greater in 14- (n = 5) and 28-day (n = 3) AAA than in saline control aortae (n = 5) (P < 0.001), which reduced between days 14 and 28. Whole-organ gamma counting confirmed greater [18F]FLT uptake in 14-day AAA (n = 9) compared to saline-infused aortae (n = 4) (P < 0.05), correlating positively with aortic volume (r = 0.71, P < 0.01). Fourteen-day AAA tissue showed increased expression of thymidine kinase-1, equilibrative nucleoside transporter (ENT)-1, ENT-2, concentrative nucleoside transporter (CNT)-1, and CNT-3 than 28-day AAA and saline control tissues (n = 3 each) (all P < 0.001). Conclusions [18F]FLT uptake is increased during the active growth phase of the AAA model compared to saline control mice and late-stage AAA.

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Efficacy of Simvastatin in Reducing Aortic Dilatation in Mouse Models of Abdominal Aortic Aneurysm

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-010-6262-8 ◽

2010 ◽

Vol 24 (5-6) ◽

pp. 373-378 ◽

Cited By ~ 19

Author(s):

Jonathan Golledge ◽

Bradford Cullen ◽

Corey Moran ◽

Catherine Rush

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Mouse Models ◽

Aortic Dilatation ◽

Abdominal Aortic

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Parallel Murine and Human Aortic Wall Genomics Reveals Metabolic Reprogramming as Key Driver of Abdominal Aortic Aneurysm Progression

Journal of the American Heart Association ◽

10.1161/jaha.120.020231 ◽

2021 ◽

Author(s):

Gabor Gäbel ◽

Bernd H. Northoff ◽

Amanda Balboa ◽

Mediha Becirovic‐ Agic ◽

Marcelo Petri ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Clinical Success ◽

Metabolic Reprogramming ◽

Histological Evaluation ◽

Aortic Dilatation ◽

Pancreatic Elastase ◽

Abdominal Aortic ◽

Porcine Pancreatic Elastase ◽

The Impact

Background While numerous interventions effectively interfered with abdominal aortic aneurysm (AAA) formation/progression in preclinical models, none of the successes translated into clinical success. Hence, a systematic exploration of parallel and divergent processes in clinical AAA disease and its 2 primary models (the porcine pancreatic elastase and angiotensin‐II infusion [AngII] murine model) was performed to identify mechanisms relevant for aneurysm disease. Methods and Results This study combines Movat staining and pathway analysis for histological and genomic comparisons between clinical disease and its models. The impact of a notable genomic signal for metabolic reprogramming was tested in a rescue trial (AngII model) evaluating the impact of 1‐(4‐pyridinyl)‐3‐(2‐quinolinyl)‐2‐propen‐1‐one (PFK15)‐mediated interference with main glycolytic switch PFKFB3. Histological evaluation characterized the AngII model as a dissection model that is accompanied by adventitial fibrosis. The porcine pancreatic elastase model showed a transient inflammatory response and aortic dilatation, followed by stabilization and fibrosis. Normalization of the genomic responses at day 14 confirmed the self‐limiting nature of the porcine pancreatic elastase model. Clear parallel genomic responses with activated adaptive immune responses, and particularly strong signals for metabolic switching were observed in human AAA and the AngII model. Rescue intervention with the glycolysis inhibitor PFK15 in the AngII model showed that interference with the glycolytic switching quenches aneurysm formation. Conclusions Despite clear morphological contrasts, remarkable genomic parallels exist for clinical AAA disease and the AngII model. The metabolic response appears causatively involved in AAA progression and provides a novel therapeutic target. The clear transient genomic response classifies the porcine pancreatic elastase model as a disease initiation model.

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Salmonellosis associated with abdominal aortic aneurysm

Archives of Internal Medicine ◽

10.1001/archinte.134.6.1095 ◽

1974 ◽

Vol 134 (6) ◽

pp. 1095-1098 ◽

Cited By ~ 5

Author(s):

Y. S. Kanwar

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Abdominal Aortic

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Current evidence and prospects for medical treatment of abdominal aortic aneurysms

VASA ◽

10.1024/0301-1526.34.4.217 ◽

2005 ◽

Vol 34 (4) ◽

pp. 217-223 ◽

Cited By ~ 11

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.

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

VASA ◽

10.1024/0301-1526/a000895 ◽

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.

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