scholarly journals The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms

2021 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Evelyn Hutterer ◽  
Sara Hultin ◽  
Otto Bergman ◽  
Maria Forteza ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Actin Filaments ◽  
Fluid Shear Stress ◽  
Abdominal Aortic Aneurysms ◽  
Normal Diet ◽  
Aortic Aneurysms ◽  
Cell Junctions ◽  
Mechanical Forces ◽  
Linc Complex ◽  
Abdominal Aortic

Abstract Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic and arterial ECs. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provokes a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and aneurysm diameters, as well as a positive correlation between AmotL2 and YAP expression. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular disease.

scholarly journals The VE-cadherin/AmotL2 mechanosensory pathway suppresses aortic inflammation and the formation of abdominal aortic aneurysms

2021 ◽  
Author(s):  
Yuanyuan Zhang ◽  
Evelyn Hutterer ◽  
Sara Hultin ◽  
Otto Bergman ◽  
Maria J. Forteza ◽  
...  
Keyword(s):  
Nuclear Membrane ◽  
Actin Filaments ◽  
Fluid Shear Stress ◽  
Abdominal Aortic Aneurysms ◽  
Normal Diet ◽  
Aortic Aneurysms ◽  
Cell Junctions ◽  
Mechanical Forces ◽  
Linc Complex ◽  
Abdominal Aortic

Arterial endothelial cells (ECs) have the ability to respond to mechanical forces exerted by fluid shear stress. This response is of importance, as it is protective against vascular diseases such as atherosclerosis and aortic aneurysms. Mechanical forces are transmitted at the sites of adhesion to the basal membrane as well as cell-cell junctions where protein complexes connect to the cellular cytoskeleton to relay force into the cell. Here we present a novel protein complex that connects junctional VE-cadherin and radial actin filaments to the LINC complex in the nuclear membrane. We show that the scaffold protein AmotL2 is essential for the formation of radial actin filaments and the flow-induced alignment of aortic and arterial ECs. The deletion of endothelial AmotL2 alters nuclear shape as well as subcellular positioning. Molecular analysis shows that VE-cadherin is mechanically associated with the nuclear membrane via binding to AmotL2 and Actin. Furthermore, the deletion of AmotL2 in ECs provokes a pro-inflammatory response and abdominal aortic aneurysms (AAA) in the aorta of mice on a normal diet. Remarkably, transcriptome analysis of AAA samples from human patients revealed a negative correlation between AmotL2 expression and aneurysm diameters, as well as a positive correlation between AmotL2 and YAP expression. These findings provide a conceptual framework regarding how mechanotransduction in the junctions is coupled with vascular disease.

Abstract 86: Intercellular Adhesion Molecule 1 Deficiency Attenuated Angiotensin II--Induced Abdominal Aortic Aneurysms in Apolipoprotein E--Deficient Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Haruhito A Uchida ◽  
Ryoko Umebayashi ◽  
Yuki Kakio ◽  
Kenichi Shikata ◽  
Hirofumi Makino
Keyword(s):  
Body Weight ◽  
Angiotensin Ii ◽  
Abdominal Aortic Aneurysms ◽  
Normal Diet ◽  
Aortic Aneurysms ◽  
Intercellular Adhesion Molecule ◽  
Intercellular Adhesion Molecule 1 ◽  
Abdominal Aortic ◽  
Deficient Mice ◽  
Mini Pump

Objective: Chronic infusion of angiotensin II (AngII) augments the development of abdominal aortic aneurysms (AAAs) in hypercholesterolemic mice. Several studies have suggested that intercellular adhesion molecule 1 (ICAM-1) expression increases in association with AAA formation. The aim of the study was to define whether ICAM deficiency influenced AngII-induced AAA formation. Methods and Results: Apolipoprotein E deficient (apoE -/-) mice were cross-bred with ICAM-1 deficient mice. Male apoE -/- mice fed a normal diet and infused subcutaneously with saline or AngII (1,000 ng/kg/min) via osmotic mini pump for 1 week. AngII infusion increased aortic ICAM-1 protein. Male apoE -/- mice that were either ICAM-1 +/+ or -/- were fed a normal diet and infused subcutaneously with AngII (1,000 ng/kg/min) via osmotic mini pump for 4 weeks. Total ICAM-1 deficiency had no significant effect on body weight, total cholesterol concentrations, or systolic blood pressures prior to and during AngII infusion. AngII induced expansion of ex vivo maximal diameters of abdominal aortas was attenuated significantly in ICAM-1 deficient mice (ICAM-1 +/+, 1.78 ± 0.20 mm; ICAM-1 -/-, 1.07 ± 0.03 mm, P < 0.0001). ICAM-1 deficiency also reduced significantly the incidence of AngII-induced AAAs (ICAM-1 +/+, 76%; ICAM-1 -/-, 13%, P < 0.0001). Furthermore, bone-marrow transplantation was performed to develop chimeric mice that were ICAM-1 +/+ or -/- in donor cells and ICAM-1 +/+ or -/- in recipient cells. ICAM-1 deficiency in either donor or recipient cells had no effect on body weight, total cholesterol concentrations, or systolic blood pressure. Recipient ICAM-1 deficiency significantly attenuated the incidence of AngII-induced AAA formation (ICAM-1 +/+, 67%; ICAM-1 -/-, 19%, P = 0.0008). Furthermore, lack of ICAM-1 reduced AngII-induced aortic MMP-2 activation (P < 0.05). Conclusion: ICAM-1 deficiency attenuated AngII-induced AAAs in male apoE -/- mice.

scholarly journals Hypercholesterolemia Accelerates Both the Initiation and Progression of Angiotensin II-induced Abdominal Aortic Aneurysms

2020 ◽  
Author(s):  
Jing Liu ◽  
Hisashi Sawada ◽  
Deborah A. Howatt ◽  
Jessica J. Moorleghen ◽  
Olga Vsevolozhskaya ◽  
...  
Keyword(s):  
Plasma Cholesterol ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Abdominal Aortic Aneurysms ◽  
Normal Diet ◽  
Western Diet ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Normal Laboratory

ABSTRACTObjectiveThis study determined whether hypercholesterolemia would contribute to both the initiation and progression of angiotensin (Ang)II-induced abdominal aortic aneurysms (AAAs) in mice.Methods and ResultsTo determine whether hypercholesterolemia accelerates the initiation of AAAs, male low-density lipoprotein (LDL) receptor -/- mice were either fed one week of Western diet prior to starting AngII infusion or initiated Western diet one week after starting AngII infusion. During the first week of AngII infusion, mice fed normal diet had less luminal expansion of the suprarenal aorta compared to those initiated Western diet after the first week of AngII infusion. The two groups achieved comparable luminal dilation on week 2 through week 6 of AngII infusion as monitored by ultrasound. To determine whether hypercholesterolemia contributed to the progression of established AAAs, male LDL receptor -/- mice were fed Western diet and infused with AngII for 4 weeks. Mice with established AAAs were then stratified into two groups based on luminal diameters measured by ultrasound. While AngII infusion was continued for another 8 weeks in both groups, mice in one group were continuously fed Western diet, but diet in the other group was switched to normal laboratory diet. In the latter group, plasma cholesterol concentrations were reduced rapidly to approximately 500 mg/dl within one week after the diet was switched from Western diet to normal laboratory diet. Luminal expansion progressed constantly in mice continuously fed Western diet, whereas no continuous expansion was detected in mice that were switched to normal laboratory diet.ConclusionsHypercholesterolemia accelerates both the initiation of AAAs and progression of established AAAs in AngII-infused male LDL receptor -/- mice.Clinical RelevanceHypercholesterolemia is modestly associated with AAAs in observational or retrospective clinical studies. It is not feasible to study whether hypercholesterolemia contributes to the initiation of AAAs or progression of established AAAs in human. This study using AngII-induced AAA mouse model provides solid evidence that hypercholesterolemia contributes to both the initiation and progression of AAAs, supporting that statin therapy at any stage of AAA development may be beneficial to hypercholesterolemic patients with AAAs.

Ruptured abdominal aortic aneurysms: Clinical presentation in Auckland 1993-1997

2001 ◽  
Vol 71 (6) ◽  
pp. 341-344
Author(s):  
Johanna Rose ◽  
Ian Civil ◽  
Timothy Koelmeyer ◽  
David Haydock ◽  
Dave Adams
Keyword(s):  
Clinical Presentation ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Ruptured Abdominal Aortic Aneurysms

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.

Statin therapy for patients with abdominal aortic aneurysms

VASA ◽  
2012 ◽  
Vol 41 (1) ◽  
pp. 3-4
Author(s):  
Diehm ◽  
Diehm ◽  
Dick
Keyword(s):  
Statin Therapy ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Abdominal Aortic

Endovascular management of ruptured abdominal aortic aneurysms and acute aortic dissections

VASA ◽  
2019 ◽  
Vol 48 (1) ◽  
pp. 35-46
Author(s):  
Stephen Hofmeister ◽  
Matthew B. Thomas ◽  
Joseph Paulisin ◽  
Nicolas J. Mouawad
Keyword(s):  
Abdominal Aortic Aneurysms ◽  
Rapid Identification ◽  
Aortic Aneurysms ◽  
Endovascular Interventions ◽  
Current State ◽  
Technological Advances ◽  
Abdominal Aortic ◽  
Ruptured Abdominal Aortic Aneurysms ◽  
Vascular Emergencies ◽  
Aortic Dissections

Abstract. The management of vascular emergencies is dependent on rapid identification and confirmation of the diagnosis with concurrent patient stabilization prior to immediate transfer to the operating suite. A variety of technological advances in diagnostic imaging as well as the advent of minimally invasive endovascular interventions have shifted the contemporary treatment algorithms of such pathologies. This review provides a comprehensive discussion on the current state and future trends in the management of ruptured abdominal aortic aneurysms as well as acute aortic dissections.

Stents for the Treatment of Aortic Aneurysms

1999 ◽  
Vol 82 (S 01) ◽  
pp. 171-175 ◽  
Author(s):  
D. Ebert ◽  
M. Langer ◽  
P. Uhrmeister
Keyword(s):  
Endovascular Treatment ◽  
Endovascular Repair ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Imaging Modalities ◽  
Exclusion Criteria ◽  
Multicenter Studies ◽  
Abdominal Aortic ◽  
First Results

SummaryThe endovascular treatment of abdominal aortic aneurysms has generated a great deal of interest since the early 1990s, and many different devices are currently available. The procedure of endovascular repair has been evaluated in many institutions and the different devices are compared. The first results were encouraging, but complications like endoleak, dislocation or thrombosis of the graft occurred. By the available devices the stent application is only promising, if the known exclusion criteria are strictly respected. Therefore a careful preinterventional assessment of the patient by different imaging modalities is necessary. As the available results up to now are preliminary and the durability of the devices has to be controlled, multicenter studies are required to improve the devices and observe their long- term success in the exclusion of abdominal aortic aneurysms.

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