scholarly journals Early Morphofunctional Changes in AngII-Infused Mice Contribute to Regional Onset of Aortic Aneurysm and Dissection

2020 ◽  
Vol 57 (6) ◽  
pp. 367-375
Author(s):  
Lydia Aslanidou ◽  
Bram Trachet ◽  
Linda Sasset ◽  
Goran Lovric ◽  
Nikolaos Stergiopulos ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Abdominal Aorta ◽  
Vascular Reactivity ◽  
Ex Vivo ◽  
Aortic Aneurysms ◽  
Microstructural Damage ◽  
Suprarenal Aorta ◽  
Aortic Aneurysm And Dissection

Aortic aneurysms and dissections are silent and lethal conditions, whose pathogenesis remains incompletely understood. Although angiotensin II (AngII)-infused ApoE−/− mice have been widely used to study aortic aneurysm and dissection, early morphofunctional alterations preceding the onset of these conditions remain unknown. The goal of this study was to unveil early morphofunctional changes underlying the onset of aneurysm and dissection. At 3 days post-AngII infusion, suprarenal abdominal aorta presented significant volumetric dilatation and microstructural damage. Ex vivo assessment of vascular reactivity of the suprarenal dissection-prone aorta and its side branches, showed an endothelial and contractile dysfunctions that were severe in the suprarenal aorta, moderate distally, and absent in the side branches, mirroring the susceptibility to dissection of these different vascular segments. Early and specific morphofunctional changes of the suprarenal aorta may contribute to the regional onset of aortic aneurysm and dissection by exacerbating the biomechanical burden arising from its side branches.

Abstract 12726: Crucial Role of Jak2 V617f-positive Myeloproliferative Neoplasm in the Development of Aortic Aneurysm

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Tetsuro Yokokawa ◽  
Tomofumi Misaka ◽  
Yusuke KIMISHIMA ◽  
Kento Wada ◽  
Keiji Minakawa ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Mrna Expression ◽  
Abdominal Aorta ◽  
Myeloproliferative Neoplasms ◽  
Myeloproliferative Neoplasm ◽  
Jak2 V617f ◽  
Vascular Complication ◽  
The Impact

Objective: To investigate the impact of hematopoietic JAK2V617F, which causes myeloproliferative neoplasms (MPNs), on the development of aortic aneurysm (AA). Approach and Results: We applied a bone marrow transplantation (BMT) strategy using the donor cells from Jak2 V617F transgenic (JAK2 V617F ) mice into the lethally irradiated apolipoprotein E-deficient mice. To induce the AA formation and progression, the recipient mice (BMT mice) were subjected to continuous angiotensin II infusion. Abdominal aortic diameter in JAK2 V617F -BMT mice was significantly enlarged compared to the control wild-type (WT)-BMT mice in response to angiotensin II. The incidence of abdominal AA was significantly higher in JAK2 V617F -BMT mice than in WT-BMT mice. Hematopoietic JAK2V617F accelerated aortic elastic lamina degradation as well as activation of matrix metalloproteinase (MMP)-2 and MMP-9 in the abdominal aorta. The numbers of CD68 + macrophages and Ly6B.2 + neutrophils and cytokine expressions such as Ccl6 and Tgfb1 were significantly increased in the abdominal aorta of JAK2 V617F -BMT mice accompanied by STAT3 activation. Bone marrow-derived macrophages carrying JAK2V617F showed elevations of both Mmp2 and Mmp9 mRNA expression. Finally, we found that 23% of MPN patients with JAK2 V617F mutation showed the presence of AA and increases in TGFB3 and IL-8 mRNA expression of the peripheral leukocytes. Conclusions: Hematopoietic JAK2V617F was involved in the development of AA through increases in the infiltration of inflammatory cells and MMP activation. Our findings provide a novel feature of vascular complication of AA in MPNs due to constitutive activation of the hematopoietic JAK-STAT pathway.

Abdominal aortic aneurysm screening programme

2019 ◽  
Vol 13 (9) ◽  
pp. 430-434
Author(s):  
Ian Peate
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aorta ◽  
Screening Programme ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Ultrasound Scan ◽  
Abdominal Aneurysm ◽  
Abdominal Aortic ◽  
The Uk

This is the second article in a series of articles regarding screening programmes. In this article, an overview of the abdominal aorta is provided. The article also considers the abdominal aortic aneurysm screening programme. Aortic abdominal aneurysm is described. The majority of abdominal aortic aneurysms are asymptomatic; however, if there are any symptoms, these are explained. All four UK countries offer men aged 65 years and over a screening opportunity using an ultrasound scan, the fundamental aspects of abdominal aortic aneurysm screening programmes is offered. It is emphasised that screening is not mandatory in the UK; the man has a right to decline the invitation to attend any screening programme.

scholarly journals High serum thrombospondin-1 concentration is associated with slower abdominal aortic aneurysm growth and deficiency of thrombospondin-1 promotes angiotensin II induced aortic aneurysm in mice

2017 ◽  
Vol 131 (12) ◽  
pp. 1261-1281 ◽  
Author(s):  
Smriti Murali Krishna ◽  
Sai Wang Seto ◽  
Roby Jose ◽  
Jiaze Li ◽  
Joseph Moxon ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Ex Vivo ◽  
High Serum ◽  
Matricellular Protein ◽  
Body Tissues ◽  
Age Related ◽  
Abdominal Aortic ◽  
Thrombospondin 1

Abdominal aortic aneurysm (AAA) is a common age-related vascular disease characterized by progressive weakening and dilatation of the aortic wall. Thrombospondin-1 (TSP-1; gene Thbs1) is a member of the matricellular protein family important in the control of extracellular matrix (ECM) remodelling. In the present study, the association of serum TSP-1 concentration with AAA progression was assessed in 276 men that underwent repeated ultrasound for a median 5.5 years. AAA growth was negatively correlated with serum TSP-1 concentration (Spearman’s rho −0.129, P=0.033). Men with TSP-1 in the highest quartile had a reduced likelihood of AAA growth greater than median during follow-up (OR: 0.40; 95% confidence interval (CI): 0.19–0.84, P=0.016, adjusted for other risk factors). Immunohistochemical staining for TSP-1 was reduced in AAA body tissues compared with the relatively normal AAA neck. To further assess the role of TSP-1 in AAA initiation and progression, combined TSP-1 and apolipoprotein deficient (Thbs1−/−ApoE−/−, n=20) and control mice (ApoE−/−, n=20) were infused subcutaneously with angiotensin II (AngII) for 28 days. Following AngII infusion, Thbs1−/− ApoE−/− mice had larger AAAs by ultrasound (P=0.024) and ex vivo morphometry measurement (P=0.006). The Thbs1−/−ApoE−/− mice also showed increased elastin filament degradation along with elevated systemic levels and aortic expression of matrix metalloproteinase (MMP)-9. Suprarenal aortic segments and vascular smooth muscle cells (VSMCs) isolated from Thbs1−/−ApoE−/− mice showed reduced collagen 3A1 gene expression. Furthermore, Thbs1−/−ApoE−/− mice had reduced aortic expression of low-density lipoprotein (LDL) receptor-related protein 1. Collectively, findings from the present study suggest that TSP-1 deficiency promotes maladaptive remodelling of the ECM leading to accelerated AAA progression.

scholarly journals Effect of Doxycycline on Survival in Abdominal Aortic Aneurysms in a Mouse Model

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lisa C. Adams ◽  
Julia Brangsch ◽  
Jan O. Kaufmann ◽  
Dilyana B. Mangarova ◽  
Jana Moeckel ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ex Vivo ◽  
Endothelial Damage ◽  
Aortic Aneurysms ◽  
Clinical Dose ◽  
Doxycycline Treatment ◽  
Abdominal Aortic ◽  
Significant Difference ◽  
Aneurysm Growth

Background. Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE−/− model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment. Methods. Nine ApoE−/− mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE−/− animals without doxycycline treatment. Differences in mortality were also investigated between these groups. Results. In a previous study, we found that approximately 25% of angiotensin II-infused ApoE−/− mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE−/− mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE−/− mice showed significantly lower contrast-to-noise (CNR) values ( p = 0.017 ) in MRI compared to ApoE−/− mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining (R2 = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment. Conclusion. The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth.

scholarly journals Association of osteoprotegerin with ascending aortic dissection

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Goliopoulou ◽  
A Antonopoulos ◽  
E Oikonomou ◽  
A Miliou ◽  
P Theofilis ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Aortic Dissection ◽  
Survival Rates ◽  
Aortic Disease ◽  
Aortic Aneurysms ◽  
Control Group ◽  
Aortic Dilatation ◽  
Serum Samples ◽  
Significant Difference ◽  
Aortic Aneurysm And Dissection

Abstract Background Thoracic aortic dissections are among the cardiovascular diseases with the highest mortality rates. Their often belated diagnosis and, hence, poor prognosis call for further research of their pathophysiology and possible biomarkers that will aid early diagnosis and increase survival rates. Osteoprotegerin is a known biomarker in cardiovascular disease, but it is yet to be determined whether it participates in aortic disease and thoracic aortic dissection in particular. Purpose This clinical study aimed at researching the role of osteoprotegerin in thoracic aortic aneurysm and dissection. Methods We compared three groups of patients; 20 patients with ascending aortic aneurysm (AAA), 10 patients with acute ascending aortic dissection (AAD) and 16 patients with normal aortic diameter undergoing cardiac surgery for other indication (control group). Serum samples were obtained from patients before surgery and osteoprotegerin levels were measured using the ELISA method. Results One-way analysis of variance revealed a significant association between the examined groups of patients and levels of osteoprotegerin (AAD: 62.72±44.53 pmol/L, AAA: 33.43±8.08 pmol/L, Control: 48.61±29.47 pmol/L, p=0.03). Importantly, after post-hoc analysis osteoprotegerin levels were found to be increased in patients with AAD compared to patients with uncomplicated AAA (62.72±44.53 pmol/L vs 33.43±8.08 pmol/L, p=0.03) (Figure 1), whereas there was no statistically significant difference between patients with AAA and the control group (33.43±8.08 pmol/L vs 48.61±29.47 pmol/L, p=0.34). Conclusions These findings suggest that osteoprotegerin may participate in the pathophysiology of aortic dissection but not in mechanisms of aortic dilatation. Therefore, detection of elevated osteoprotegerin levels in patients with diagnosed ascending aortic aneurysms might suggest an increased probability of dissection and, therefore, aid the decision-making process. Figure 1 Funding Acknowledgement Type of funding source: None

scholarly journals Prevention of CaCl2-induced aortic inflammation and subsequent aneurysm formation by the CCL3–CCR5 axis

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yuko Ishida ◽  
Yumi Kuninaka ◽  
Mizuho Nosaka ◽  
Akihiko Kimura ◽  
Akira Taruya ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Abdominal Aorta ◽  
Chemokine Receptor ◽  
Wild Type ◽  
Specific Receptor ◽  
Cytokines And Chemokines ◽  
Abdominal Aortic ◽  
Enhanced Expression

AbstractInflammatory mediators such as cytokines and chemokines are crucially involved in the development of abdominal aortic aneurysm (AAA). Here we report that CaCl2 application into abdominal aorta induces AAA with intra-aortic infiltration of macrophages as well as enhanced expression of chemokine (C-C motif) ligand 3 (CCL3) and MMP-9. Moreover, infiltrating macrophages express C-C chemokine receptor 5 (CCR5, a specific receptor for CCL3) and MMP-9. Both Ccl3−/− mice and Ccr5−/− but not Ccr1−/− mice exhibit exaggerated CaCl2-inducced AAA with augmented macrophage infiltration and MMP-9 expression. Similar observations are also obtained on an angiotensin II-induced AAA model. Immunoneutralization of CCL3 mimics the phenotypes observed in CaCl2-treated Ccl3−/− mice. On the contrary, CCL3 treatment attenuates CaCl2-induced AAA in both wild-type and Ccl3−/− mice. Consistently, we find that the CCL3–CCR5 axis suppresses PMA-induced enhancement of MMP-9 expression in macrophages. Thus, CCL3 can be effective to prevent the development of CaCl2-induced AAA by suppressing MMP-9 expression.

Abstract 243: Adiponectin Inhibits Angiotensin II-induced Abdominal Aortic Aneurysm Formation

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Emina Vorkapic ◽  
Dick Wågsäter ◽  
Caroline Van Stijn ◽  
Jason Kim ◽  
Per Eriksson ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Abdominal Aorta ◽  
Recombinant Adenovirus ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Green Fluorescence Protein ◽  
Aortic Aneurysms ◽  
Plasma Adiponectin ◽  
Abdominal Aortic ◽  
The Impact

BACKGROUND Abdominal aortic aneurysms (AAA) are characterized by inflammation, loss of smooth muscle cells (SMC) and degradation of extracellular matrix in the vessel wall. Adiponectin, an adipokine produced by adipose tissue, exerts profound anti-inflammatory and anti-atherogenic effects on vascular cells. However, the role of adiponectin on AAA has not been studied. We investigated the impact of increased plasma adiponectin levels on angiotensin II (AngII)-induced AAA formation in mice. METHOD AND RESULTS Male low-density lipoprotein receptor-deficient (LDLR -/- ) mice fed on a high-fat diet were infused with AngII (25 mg/kg/min) for 8 weeks to induce AAA. Mice infused with saline was used as controls. A recombinant adenoviral vector encoding mouse adiponectin (Ad-APN) was injected intravenously to induce adiponectin expression. A recombinant adenovirus expressing green fluorescence protein (GFP) was used as a control (Ad-GFP). Eight weeks after injection, plasma adiponectin levels were 10-fold higher (253.9±59.0 μg/mL) in Ad-APN mice compared to Ad-GFP mice (25.2±3.8 μg/mL, P<0.001). Aortic diameter was significantly reduced in Ad-APN mice compared to Ad-GFP mice (60% reduction). This was accompanied by decreased frequency and size of abdominal atherosclerotic lesions in Ad-APN mice compared to Ad-GFP mice. Histologically, elastin was degraded in all AngII-infused mice compared to saline-infused mice. However elastin was more preserved in Ad-APN mice compared to Ad-GFP mice (P<0.05). Gene expression analysis of the abdominal aorta revealed a decrease of CD3e (P<0.05) but no profound changes in inflammatory genes, IL-6, TNF-α and CD68. Decreased mRNA expression of the SMC marker SM22α was observed in all AngII-infused mice compared to saline-infused mice. Expression of SM22α was two-fold higher in the abdominal aorta in Ad-APN mice than in Ad-GFP mice (P<0.05). CONCLUSION These results provide first evidence that adiponectin overexpression significantly inhibits AngII-induced AAA formation in LDLR -/- mice. The protective actions of adiponectin appear to be mediated, in part, through preservation of SMC content and elastin in the vascular wall. The mechanisms of adiponectin inhibiting AAA formation deserve further attention.

Abstract 461: Cilnidipine Attenuated Angiotensin II-induced Abdominal Aortic Aneurysms in Apolipoprotein E-deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Yuki Kakio ◽  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Jun Wada
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Angiotensin Ii ◽  
Apolipoprotein E ◽  
Ex Vivo ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Osmotic Minipumps ◽  
Abdominal Aortic ◽  
Deficient Mice

Objective: Chronic infusion of angiotensin II (AngII) promotes development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Previous studies have shown that local inflammation and increased oxidative stress plays an important role on formation of AAAs. In addition, it is reported that voltage-dependent N-type Ca2+ channels in endothelial cells contribute to oxidative stress-related endothelial dysfunction induced by AngII in mice. Therefore, we hypothesized that cilnidipine, an N/L-type calcium channel blocker, exerts vasoprotective effect by inhibiting inflammation and superoxide generation in mice. The purpose of this study was to evaluate whether cilnidipine influenced AngII-induced AAAs. Methods and Results: Male apolipoprotein E deficient mice (8-12 weeks old) were fed a normal laboratory diet. Mice were infused subcutaneously with either cilnidipine or vehicle by osmotic minipumps. Three days later, mice were also infused subcutaneously with either AngII (1,000 ng/kg/min, n = 14-16) or saline (n = 4) each by osmotic minipumps for 4 weeks. AngII increased systolic blood pressure. Cilnidipine decreased blood pressure in AngII-infused mice, but had not effect during saline infusion. AngII infusion did not alter serum cholesterol concentrations. However, cilnidipine slightly decreased serumcholesterol concentrations in AngII-infused mice. Cilnidipine had no effect on body weights, heart rates, and urine total protein, but mildly restored plasma renin activity that were suppressed by AngII infusion. Cilnidipine did not affect ex vivo measurement of maximal diameter of abdominal aorta (1.04 ± 0.09 mm vs 1.11 ± 0.06 mm, n.s.) in saline infused mice. AngII infusion significantly increased ex vivo maximal diameters of abdominal aortas, but was attenuated by cilnidipine (1.79 ± 0.59 mm vs 1.26 ± 0.38 mm, P < 0.05). In addition, cilnidipine significantly reduced the incidence of AngII-induced AAAs (Cilnidipine: 38 %, Vehicle: 88 %; P < 0.05). Furthermore, gelatin zymography demonstrated that cilnidipine diminished AngII-induced increase in aortic MMP-9 protein abundance. Conclusion: Cilnidipine attenuated AngII-induced AAAs in male apolipoprotein E deficient mice.

scholarly journals Surgery of infrarenal inflammatory aneurysm of abdominal aorta infected with methicillin resistant Staphylococcus aureus in a patient undergoing haemodialysis

2008 ◽  
Vol 136 (9-10) ◽  
pp. 529-532 ◽  
Author(s):  
Srdjan Babic ◽  
Petar Popov ◽  
Miroslav Milicic ◽  
Nenad Ilijevski ◽  
Dragoslav Nenezic ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Abdominal Aorta ◽  
Defense Mechanism ◽  
Immune Defense ◽  
Aortic Aneurysms ◽  
Inflammatory Aneurysm ◽  
Abdominal Aortic ◽  
Inflammatory Abdominal Aortic Aneurysm

INTRODUCTION Inflammatory abdominal aortic aneurysm accounts for 5% to 10% of all cases of abdominal aortic aneurysm and differs from typical atherosclerotic abdominal aortic aneurysm in many important ways. Although both inflammatory and atherosclerotic abdominal aortic aneurysms most commonly affect the infrarenal portion of the abdominal aorta, patients with the inflammatory variant are younger and usually symptomatic, chiefly from back or abdominal pain. Unlike patients with atherosclerotic abdominal aortic aneurysm, most with the inflammatory variant have an elevated erythrocyte sedimentation rate or abnormalities of other serum inflammatory markers. Computed tomography and magnetic resonance imaging are both sensitive for demonstrating the cuff of soft tissue inflammation surrounding the aneurysm that is characteristic of inflammatory abdominal aortic aneurysm. Inflammatory abdominal aortic aneurysm can be primarily infected by degenaration of an infected artery (in less than 1% of cases), or can become secondary infected in the already existing aneurysm. Secondary infection of the pre-existing aneurysm has big influence on treatment choice, but is also rare. Clinically non-symptomatic infection, also known as bacterial collonisation, can be very frequent, regarding a greatly increased number of positive intraoperative findings (10-15%). Prolonged intravascular catheterization, vascular grafting, repeated punctures with large bore needles, and decreased immune defense mechanism make uraemic patients undergoing hemodialysis more likely to develop Staphylococcus aureus bacteraemia and its complications. CASE OUTLINE The case shows a gigantic inflammatory aneurysm of the abdominal aorta, localized infrarenally, which was solved successfully by resection of the aneurysm of the abdominal aorta, and interposition of Dacron tubular graft 22 mm. Bacterial examination of the aneurysmal sac was positive: methicillin-resistent Staphylococcus aureus was detected. CONCLUSION There were no postoperative complications, and the final outcome was fully satisfactory. Control CT scans after 3, 6 and 12 months were regular, with signs of regression fibrosis of the retroperitoneum.

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