scholarly journals Lower levels of Caveolin-1 and higher levels of endothelial nitric oxide synthase are observed in abdominal aortic aneurysm patients treated with simvastatin

2018 ◽  
Vol 65 (1) ◽  
pp. 111-118 ◽  
Author(s):  
Karolina Kowalska ◽  
Dominika E Habrowska-Górczyńska ◽  
Christoph Neumayer ◽  
Michael Bolliger ◽  
Christoph Domenig ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Enos Expression ◽  
Toll Like Receptor 4 ◽  
Simvastatin Treatment ◽  
Caveolin 1 ◽  
Abdominal Aortic ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

This study was undertaken to verify if simvastatin modulates Cav-1/eNOS expression and if this modulation is associated with changes in pro- and anti-inflammatory cytokines and Toll-like receptor 4 (TLR4) in abdominal aortic aneurysm (AAA). It was 1:2 case-control study of non-statin (n=12) and simvastatin-treated patients (n=24) who underwent open AAA repair. Simvastatin treatment significantly and dose-dependently decreased Cav-1 and increased eNOS expression in AAA wall (p<0.05 and p<0.01, respectively). The changes in Cav-1 and eNOS were associated with a trend towards decreased concentration of IL-6 and IL-17 (p>0.05) and increased concentration of IL-10 (p=0.055) but not with TLR4 expression suggesting other mechanism of simvastatin influence on Cav-1 and eNOS in AAA wall. Simvastatin may modulate Cav-1 and eNOS expression in aneurysmal wall indicating a new beneficial role of statins in AAA patients.

Abstract 122: STAT3 Mediates Toll-Like Receptor 4--Dependent Abdominal Aortic Aneurysm Formation in Angiotensin II--Treated ApoE-/- Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Zhexue Qin ◽  
Ho-Jin Park ◽  
Debbie Beasley ◽  
Jonas Galper ◽  
Yali Zhang
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Diameter ◽  
Tlr4 Expression ◽  
Toll Like Receptor 4 ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
Increased Activity ◽  
Stimulation Of

Abdominal aortic aneurysm (AAAs) is a life threatening disease and currently the only treatment is surgical or endovascular repair. Using an animal model for AngiotensinII (AngII) mediated AAA formation in the ApoE-/- mouse, we demonstrate that AAA formation is dependent on the activation of the JAK/STAT pathway. STAT3 activity was increased in the abdominal aortas of Ang II treated ApoE-/- mice. Treatment of ApoE-/- mice with AngII and the p-STAT3 inhibitor S3I-201 decreased the incidence of AAA formation and aortic diameter by greater than 50% compared to placebo. While AngII treatment increased activity of MMP2 and MMP9 in aortas of ApoE-/- mice, S3I-201 treatment inhibited p-STAT3 stimulation and decreased MMP2 and MMP9 activity to levels similar to those in control aortas. The increase in p-STAT3 levels and the secretion of MMP2 and MMP9 in AngII treated bone marrow derived macrophages (BDMs) from ApoE-/- mice was inhibited by pretreatment with S3I-201. Interestingly, AngII stimulated TLR4 expression in AAAs and in BDMs from ApoE-/- mice. Based on these findings we determined the role of TLR4 on AAA formation and p-STAT3 stimulation in ApoE-/-TLR4-/- mice. The incidence of AAA formation, increase in aortic diameter and MMP2 and MMP9 activity were markedly decreased in AngII treated ApoE-/-TLR4-/- mice compared to ApoE-/- controls. Importantly, AngII stimulation of p-STAT3 was also decreased in ApoE-/-TLR4-/- mice compared to control. Similar effects on AngII stimulated p-STAT3 and activity of MMP2 and MMP9 were demonstrated in BMDs from ApoE-/-TLR4-/- mice. Treatment of ApoE-/- mice with the TLR4 inhibitor Eritoran (Eisai, Inc) also decreased the incidence and severity of AAAs, MMPs secretion and p-STAT3 activity. Finally, we determined that S3I-201 decreased AngII stimulated TLR4 expression in AngII treated ApoE-/- mice and in BDM from ApoE-/- mice compared to placebo. These data supported the conclusion that AngII stimulation of AAAs is mediated via a TLR4 dependent activation of p-STAT3 and that both p-STAT3 and TLR4 might be potential therapeutic targets for the treatment of AAAs.

scholarly journals Circulating tetrahydrobiopterin as a novel biomarker for abdominal aortic aneurysm

2014 ◽  
Vol 307 (11) ◽  
pp. H1559-H1564 ◽  
Author(s):  
Kin Lung Siu ◽  
Hua Cai
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Folic Acid ◽  
Aortic Aneurysm ◽  
Response To Treatment ◽  
Tissue Levels ◽  
Abdominal Aortic ◽  
Significant Linear Correlation ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
The Relationship

Rupture of abdominal aortic aneurysm (AAA) is unpredictable and lethal. A clinically valid biomarker to monitor the disease has not been available. Based on our recent discoveries that uncoupled endothelial nitric oxide synthase (eNOS)/tetrahydrobiopterin deficiency plays a causal role in various models of AAA, the present study examined the relationship between circulating and tissue levels of tetrahydrobiopterin (H4B) in angiotensin II-infused hyperphenylalaninemia (hph-1) and apoE null mice. For apoE null mice, tissue and plasma H4B levels decreased time dependently, to 2.69 ± 0.15 and 1.99 ± 0.06 pmol/mg, respectively (from 4.86 ± 0.32 and 3.31 ± 0.13 pmol/mg at baseline) by week 3, when aneurysms developed. For hph-1 mice, tissue and plasma H4B levels decreased significantly to 1.02 ± 0.10 and 0.98 ± 0.09 pmol/mg, respectively (from 1.84 ± 0.18 and 1.48 ± 0.12 pmol/mg at baseline), by week 1, when aneurysms developed. Oral folic acid administration, which has been shown to improve aortic H4B levels to completely prevent or markedly decrease the incidence of AAA, significantly increased tissue and plasma H4B levels in both animal models starting at week 1. The two H4B measurements at all conditions showed significant linear correlation, suggesting that plasma H4B accurately predicts its tissue levels when H4B is either reduced or enhanced. Together, these data demonstrate that H4B levels decrease with AAA development and increase with folic acid treatment in two different murine models of AAA and that plasma H4B levels accurately reflect H4B levels in the tissue, suggesting that circulating H4B levels may be used clinically as a novel and powerful biomarker for the development and response to treatment of AAA.

scholarly journals Prospect of positron emission tomography for abdominal aortic aneurysm risk stratification

2021 ◽  
Author(s):  
Richa Gandhi ◽  
Michael Bell ◽  
Marc Bailey ◽  
Charalampos Tsoumpas
Keyword(s):  
Positron Emission Tomography ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Risk Stratification ◽  
Patient Management ◽  
Emission Tomography ◽  
Clinical Implementation ◽  
Positron Emission ◽  
Abdominal Aortic

AbstractAbdominal aortic aneurysm (AAA) disease is characterized by an asymptomatic, permanent, focal dilatation of the abdominal aorta progressing towards rupture, which confers significant mortality. Patient management and surgical decisions rely on aortic diameter measurements via abdominal ultrasound surveillance. However, AAA rupture can occur at small diameters or may never occur at large diameters, implying that anatomical size is not necessarily a sufficient indicator. Molecular imaging may help identify high-risk patients through AAA evaluation independent of aneurysm size, and there is the question of the potential role of positron emission tomography (PET) and emerging role of novel radiotracers for AAA. Therefore, this review summarizes PET studies conducted in the last 10 years and discusses the usefulness of PET radiotracers for AAA risk stratification. The most frequently reported radiotracer was [18F]fluorodeoxyglucose, indicating inflammatory activity and reflecting the biomechanical properties of AAA. Emerging radiotracers include [18F]-labeled sodium fluoride, a calcification marker, [64Cu]DOTA-ECL1i, an indicator of chemokine receptor type 2 expression, and [18F]fluorothymidine, a marker of cell proliferation. For novel radiotracers, preliminary trials in patients are warranted before their widespread clinical implementation. AAA rupture risk is challenging to evaluate; therefore, clinicians may benefit from PET-based risk assessment to guide patient management and surgical decisions.

scholarly journals The Role of Geometric Parameters in the Prediction of Abdominal Aortic Aneurysm Wall Stress

2010 ◽  
Vol 39 (1) ◽  
pp. 42-48 ◽  
Author(s):  
E. Georgakarakos ◽  
C.V. Ioannou ◽  
Y. Kamarianakis ◽  
Y. Papaharilaou ◽  
T. Kostas ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Wall Stress ◽  
Geometric Parameters ◽  
Aneurysm Wall ◽  
Abdominal Aortic ◽  
Abdominal Aortic Aneurysm Wall

scholarly journals Role of vascular endothelial growth factor-A in development of abdominal aortic aneurysm

2011 ◽  
Vol 91 (2) ◽  
pp. 358-367 ◽  
Author(s):  
Hidehiro Kaneko ◽  
Toshihisa Anzai ◽  
Toshiyuki Takahashi ◽  
Takashi Kohno ◽  
Masayuki Shimoda ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Abdominal Aortic Aneurysm ◽  
Growth Factor ◽  
Aortic Aneurysm ◽  
Vascular Endothelial ◽  
Abdominal Aortic ◽  
Endothelial Growth Factor
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