scholarly journals Interaction between Angiotensin II, Osteoprotegerin, and Peroxisome Proliferator-Activated Receptor-γ in Abdominal Aortic Aneurysm

2009 ◽  
Vol 46 (3) ◽  
pp. 209-217 ◽  
Author(s):  
Corey S. Moran ◽  
Bradford Cullen ◽  
Julie H. Campbell ◽  
Jonathan Golledge
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Abdominal Aortic

scholarly journals Fibrates: A Possible Treatment Option for Patients with Abdominal Aortic Aneurysm?

Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 74
Author(s):  
Naofumi Amioka ◽  
Toru Miyoshi
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Therapeutic Agent ◽  
Therapeutic Agents ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Abdominal Aortic ◽  
Life Threatening ◽  
New Perspective ◽  
Oxidative Effects

Abdominal aortic aneurysm (AAA) is a life-threatening disease; however, there is no established treatment for patients with AAA. Fibrates are agonists of peroxisome proliferator-activated receptor alpha (PPARα) that are widely used as therapeutic agents to treat patients with hypertriglyceridemia. They can regulate the pathogenesis of AAA in multiple ways, for example, by exerting anti-inflammatory and anti-oxidative effects and suppressing the expression of matrix metalloproteinases. Previously, basic and clinical studies have evaluated the effects of fenofibrate on AAA. In this paper, we summarize the results of these studies and discuss the problems associated with using fenofibrate as a therapeutic agent for patients with AAA. In addition, we discuss a new perspective on the regulation of AAA by PPARα agonists.

scholarly journals Endothelial Cell Tetrahydrobiopterin Modulates Sensitivity to Ang (Angiotensin) II–Induced Vascular Remodeling, Blood Pressure, and Abdominal Aortic Aneurysm

Hypertension ◽  
2018 ◽  
Vol 72 (1) ◽  
pp. 128-138 ◽  
Author(s):  
Surawee Chuaiphichai ◽  
Victoria S. Rashbrook ◽  
Ashley B. Hale ◽  
Lucy Trelfa ◽  
Jyoti Patel ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Abdominal Aortic Aneurysm ◽  
Endothelial Cell ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Vascular Remodeling ◽  
Abdominal Aortic

Abstract 279: Role of Caveolin-1 in Abdominal Aortic Aneurysm induced by Angiotensin II

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Takayanagi ◽  
Kevin Crawford ◽  
Tomonori Kobayashi ◽  
Victor Rizzo ◽  
Satoru Eguchi
Keyword(s):  
Oxidative Stress ◽  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Egf Receptor ◽  
Critical Role ◽  
Membrane Microdomains ◽  
Structural Protein ◽  
Caveolin 1 ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) is a significant cause of mortality for adults aged >60 years. Accumulating evidence suggests that activation of the AT1 receptor by angiotensin II (AngII) in AAA formation. While several downstream signals and target proteins have been identified in this pathway, there is a huge void in our knowledge regarding the AngII-sensitive proximal events primarily responsible for AAA formation. We recently reported that caveolae membrane microdomains in vascular smooth muscle cells (VSMC) mediate a metalloprotease ADAM17-dependent EGF receptor (EGFR) transactivation which linked to vascular remodeling induced by AngII. Given that ADAM17 expression is one of the key features in AAA, we have tested our hypothesis that caveolin-1 (Cav1), a major structural protein of caveolae, in the vasculature plays a critical role for development of AAA via its regulation on ADAM17. 8 week old male Cav1-/- mice and the control C57Bl/6 wild-type (WT) mice were co-infused with AngII and BAPN, a lysyl oxidase inhibitor, to induce AAA. We found that Cav1-/- mice did not develop AAA compared to C57Bl/6 mice in spite of hypertension assessed by telemetry in both groups. This finding suggests that the AngII signaling essential for vascular contraction remains in place in Cav1-/- mice. We found an increased expression of ADAM17 and auto-phosphorylation of EGFR in WT abdominal aortae with aneurysms that were markedly attenuated in Cav1-/- mice infused with AngII+BAPN. Furthermore, Cav1-/- mice with the infusion showed less oxidative stress and ER stress than their WT counterparts as assessed by nitrotyrosine staining and KDEL/p-eIF2a staining, respectively. In conclusion, Cav1 and presumably vascular caveolae micro-domain appear to play a critical role in the formation of AAA in mice via regulation of the ADAM17/EGFR signaling axis and subsequent induction of ER/oxidative stress.

scholarly journals IKK Epsilon Deficiency Attenuates Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Mice by Inhibiting Inflammation, Oxidative Stress, and Apoptosis

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Hao Chai ◽  
ZhongHao Tao ◽  
YongChao Qi ◽  
HaoYu Qi ◽  
Wen Chen ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Ang Ii ◽  
Elastin Degradation ◽  
Maximal Diameter ◽  
Abdominal Aortic ◽  
Primary Mouse

Abdominal aortic aneurysm (AAA) is a vascular disorder that is considered a chronic inflammatory disease. However, the precise molecular mechanisms involved in AAA have not been fully elucidated. Recently, significant progress has been made in understanding the function and mechanism of action of inhibitor of kappa B kinase epsilon (IKKε) in inflammatory and metabolic diseases. The angiotensin II- (Ang II-) induced or pharmacological inhibitors were established to test the effects of IKKε on AAA in vivo. After mice were continuously stimulated with Ang II for 28 days, morphologically, we found that knockout of IKKε reduced AAA formation and drastically reduced maximal diameter and severity. We also observed a decrease in elastin degradation and medial destruction, which were independent of systolic blood pressure or plasma cholesterol concentrations. Western blot analyses and immunohistochemical staining were carried out to measure IKKε expression in AAA tissues and cell lines. AAA phenotype of mice was measured by ultrasound and biochemical indexes. In zymography, immunohistology staining, immunofluorescence staining, and reactive oxygen species (ROS) analysis, TUNEL assay was used to examine the effects of IKKε on AAA progression in AAA mice. IKKε deficiency significantly inhibited inflammatory macrophage infiltration, matrix metalloproteinase (MMP) activity, ROS production, and vascular smooth muscle cell (VSMC) apoptosis. We used primary mouse aortic VSMC isolated from apolipoprotein E (Apoe) −/− and Apoe−/−IKKε−/− mice. Mechanistically, IKKε deficiency blunted the activation of the ERK1/2 pathway. The IKKε inhibitor, amlexanox, has the same impact in AAA. Our results demonstrate a critical role of IKKε in AAA formation induced by Ang II in Apoe−/− mice. Targeting IKKε may constitute a novel therapeutic strategy to prevent AAA progression.

scholarly journals Caloric Restriction Exacerbates Angiotensin II–Induced Abdominal Aortic Aneurysm in the Absence of p53

Hypertension ◽  
2019 ◽  
Vol 73 (3) ◽  
pp. 547-560 ◽  
Author(s):  
Peng Gao ◽  
Hexuan Zhang ◽  
Qin Zhang ◽  
Xia Fang ◽  
Hao Wu ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Caloric Restriction ◽  
Abdominal Aortic

scholarly journals Eosinophils Protect Mice from Angiotensin-II Perfusion-Induced Abdominal Aortic Aneurysm

2020 ◽  
Author(s):  
Cong-Lin Liu ◽  
Xin Liu ◽  
Yuanyuan Zhang ◽  
Jing Liu ◽  
Chongzhe Yang ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Macrophage Polarization ◽  
Aortic Disease ◽  
Immunofluorescent Staining ◽  
Blood Eosinophil ◽  
Cationic Protein ◽  
Abdominal Aortic ◽  
M1 Macrophage

Rationale: Blood eosinophil (EOS) count and EOS cationic protein (ECP) associate with human cardiovascular diseases (CVD). Yet, whether EOS play a role in CVD remains untested. The current study detected EOS accumulation in human and murine abdominal aortic aneurysm (AAA) lesions, suggesting EOS participation in this aortic disease. Objective: To test whether and how EOS affect AAA growth. Methods and Results: Population-based randomized clinically controlled screening trials revealed higher blood EOS count in 579 male AAA patients than in 5,063 non-AAA control (0.236{plus minus}0.182 vs 0.211{plus minus}0.154, 109/L, P<0.001). Univariate (OR=1.381, P<0.001) and multivariate (OR=1.237, P=0.031) logistic regression analyses indicated that increased blood EOS count in AAA patients served as an independent risk factor of human AAA. Immunostaining and immunoblot analyses detected EOS accumulation and EOS cationic protein expression in human and murine AAA lesions. Results showed that EOS deficiency exacerbated AAA growth with increased lesion inflammatory cell contents, matrix-degrading protease activity, angiogenesis, cell proliferation and apoptosis, and smooth muscle cell (SMC) loss using angiotensin-II perfusion-induced AAA in Apoe -/- and EOS-deficient Apoe -/- ;∆dblGATA mice. EOS deficiency increased lesion chemokine expression, muted lesion expression of IL4 and EOS-associated-ribonuclease-1 (mEar1, human ECP homolog), and slanted M1 macrophage polarization. In cultured macrophages and monocytes, EOS-derived IL4 and mEar1 polarized M2 macrophages, suppressed CD11b+Ly6Chi monocytes, and increased CD11b + Ly6C lo monocytes. mEar1 treatment or adoptive transfer of EOS from WT and Il13 -/- mice, but not EOS from Il4 -/- mice, blocked AAA growth in Apoe -/- ∆dblGATA mice. Immunofluorescent staining and immunoblot analyses demonstrated a role for EOS IL4 and mEar1 in blocking NF-κB activation in macrophages, SMCs, and endothelial cells. Conclusions: EOS play a protective role in AAA by releasing IL4 and cationic proteins such as mEar1 to regulate macrophage and monocyte polarization and to block NF-κB activation in aortic inflammatory and vascular cells.

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