1,136 results match your criteria mice aaa

Adventitial recruitment of Lyve-1- macrophages drives aortic aneurysm in an angiotensin-2-based murine model.

Clin Sci (Lond) 2021 May 12. Epub 2021 May 12.

University of Toronto, Toronto, Canada.

Objective: Aortic macrophage accumulation is characteristic of the pathogenesis of abdominal aortic aneurysm (AAA) but the mechanisms of macrophage accumulation and their phenotype are poorly understood. Lyve-1+ resident aortic macrophages independently self-renew and are functionally distinct from monocyte-derived macrophages recruited during inflammation. We hypothesized that Lyve-1+ and Lyve-1- macrophages differentially contribute to aortic aneurysm. Read More

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Chemerin-9 Attenuates Experimental Abdominal Aortic Aneurysm Formation in ApoE Mice.

J Oncol 2021 17;2021:6629204. Epub 2021 Apr 17.

Department of Vascular Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Chronic inflammation plays an essential role in the pathogenesis of abdominal aortic aneurysm (AAA), a progressive segmental abdominal aortic dilation. Chemerin, a multifunctional adipocytokine, is mainly generated in the liver and adipose tissue. The combination of chemerin and chemokine-like receptor 1 (CMKLR1) has been demonstrated to promote the progression of atherosclerosis, arthritis diseases, and Crohn's disease. Read More

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Computed tomography imaging of macrophage phagocytic activity in abdominal aortic aneurysm.

Theranostics 2021 3;11(12):5876-5888. Epub 2021 Apr 3.

Cardiovascular Molecular Imaging Laboratory, Section of Cardiovascular Medicine and Yale Cardiovascular Research Center, Yale University School of Medicine, New Haven, CT (USA).

Inflammation plays a major role in the pathogenesis of several vascular pathologies, including abdominal aortic aneurysm (AAA). Evaluating the role of inflammation in AAA pathobiology and potentially outcome requires non-invasive tools for high-resolution imaging. We investigated the feasibility of X-ray computed tomography (CT) imaging of phagocytic activity using nanoparticle contrast agents to predict AAA outcome. Read More

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Systemic delivery of targeted nanotherapeutic reverses angiotensin II-induced abdominal aortic aneurysms in mice.

Sci Rep 2021 Apr 21;11(1):8584. Epub 2021 Apr 21.

Department of Bioengineering, Clemson University, 501 Rhodes Engineering Research Center, Clemson, SC, 29634, USA.

Abdominal aortic aneurysm (AAA) disease causes dilation of the aorta, leading to aortic rupture and death if not treated early. It is the 14th leading cause of death in the U.S. Read More

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Loss of FoxO3a prevents aortic aneurysm formation through maintenance of VSMC homeostasis.

Cell Death Dis 2021 Apr 7;12(4):378. Epub 2021 Apr 7.

Department of Cardiology, Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases, Ministry of Education, First Affiliated Hospital of Gannan Medical University, Gannan Medical University, University Town, Ganzhou Development District, 341000, Ganzhou, China.

Vascular smooth muscle cell (VSMC) phenotypic switching plays a critical role in the formation of abdominal aortic aneurysms (AAAs). FoxO3a is a key suppressor of VSMC homeostasis. We found that in human and animal AAA tissues, FoxO3a was upregulated, SM22α and α-smooth muscle actin (α-SMA) proteins were downregulated and synthetic phenotypic markers were upregulated, indicating that VSMC phenotypic switching occurred in these diseased tissues. Read More

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Rolipram Prevents the Formation of Abdominal Aortic Aneurysm (AAA) in Mice: PDE4B as a Target in AAA.

Antioxidants (Basel) 2021 Mar 16;10(3). Epub 2021 Mar 16.

CIBER de Enfermedades Cardiovasculares, ISCIII, 28029 Madrid, Spain.

Abdominal aortic aneurysm (AAA) is a common life-threatening condition characterized by exacerbated inflammation and the generation of reactive oxygen species. Pharmacological treatments to slow AAA progression or to prevent its rupture remain a challenge. Targeting phosphodiesterase 4 (PDE4) has been verified as an effective therapeutic strategy for an array of inflammatory conditions; however, no studies have assessed yet PDE4 in AAA. Read More

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Dynamic Remodeling of Membranes and Their Lipids during Acute Hormone-Induced Steroidogenesis in MA-10 Mouse Leydig Tumor Cells.

Int J Mol Sci 2021 Mar 4;22(5). Epub 2021 Mar 4.

The Research Institute, McGill University Health Centre, Montreal, QC H4A 3J1, Canada.

Lipids play essential roles in numerous cellular processes, including membrane remodeling, signal transduction, the modulation of hormone activity, and steroidogenesis. We chose steroidogenic MA-10 mouse tumor Leydig cells to investigate subcellular lipid localization during steroidogenesis. Electron microscopy showed that cAMP stimulation increased associations between the plasma membrane (PM) and the endoplasmic reticulum (ER) and between the ER and mitochondria. Read More

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Thymosin β4 protects against aortic aneurysm via endocytic regulation of growth factor signaling.

J Clin Invest 2021 Mar 30. Epub 2021 Mar 30.

Department of Physiology, Anatomy, and Genetics, University of Oxford, Oxford, United Kingdom.

Vascular stability and tone are maintained by contractile smooth muscle cells (VSMCs). However, injury-induced growth factors stimulate a contractile-synthetic phenotypic modulation which increases susceptibility to abdominal aortic aneurysm (AAA). As a regulator of embryonic VSMC differentiation, we hypothesised that Thymosin β4 (Tβ4) may function to maintain healthy vasculature throughout postnatal life. Read More

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The Association Between Curvature and Rupture in a Murine Model of Abdominal Aortic Aneurysm and Dissection.

Exp Mech 2021 Jan 15;61(1):203-216. Epub 2020 Sep 15.

Biomedical Engineering Program, University of South Carolina, Columbia, SC, USA.

Background: Mouse models of abdominal aortic aneurysm (AAA) and dissection have proven to be invaluable in the advancement of diagnostics and therapeutics by providing a platform to decipher response variables that are elusive in human populations. One such model involves systemic Angiotensin II (Ang-II) infusion into low density-lipoprotein receptor-deficient (LDLr-/-) mice leading to intramural thrombus formation, inflammation, matrix degradation, dilation, and dissection. Despite its effectiveness, considerable experimental variability has been observed in AAAs taken from our Ang-II infused LDLr-/- mice (n=12) with obvious dissection occurring in 3 samples, outer bulge radii ranging from 0. Read More

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January 2021

MicroRNA-23b prevents aortic aneurysm formation by inhibiting smooth muscle cell phenotypic switching via FoxO4 suppression.

Life Sci 2021 Mar 15:119092. Epub 2021 Mar 15.

Department of Cardiology, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai 519000, China. Electronic address:

Aims: Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for the formation of abdominal aortic aneurysms (AAAs). MicroRNA-23b (miR-23b) has recently been shown to play a vital role in maintaining the VSMC contractile phenotype; however, little is known about the role of miR-23b in the formation of AAAs. Here, we investigated whether miR-23b prevents AAA formation by inhibiting VSMC phenotypic switching. Read More

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Pharmacological ablation of astrocytes reduces Aβ degradation and synaptic connectivity in an ex vivo model of Alzheimer's disease.

J Neuroinflammation 2021 Mar 17;18(1):73. Epub 2021 Mar 17.

Department of Brain Sciences, Imperial College London, Hammersmith Hospital, London, W12 0NN, UK.

Background: Astrocytes provide a vital support to neurons in normal and pathological conditions. In Alzheimer's disease (AD) brains, reactive astrocytes have been found surrounding amyloid plaques, forming an astrocytic scar. However, their role and potential mechanisms whereby they affect neuroinflammation, amyloid pathology, and synaptic density in AD remain unclear. Read More

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Testosterone Metabolite 6β-Hydroxytestosterone Contributes to Angiotensin II-Induced Abdominal Aortic Aneurysms in Male Mice.

J Am Heart Assoc 2021 Apr 15;10(7):e018536. Epub 2021 Mar 15.

Department of Pharmacology Addiction Science and Toxicology College of Medicine University of Tennessee Health Science Center Memphis TN.

Background Sex is a prominent risk factor for abdominal aortic aneurysms (AAAs), and angiotensin II (Ang II) induces AAA formation to a greater degree in male than in female mice. We previously reported that cytochrome P450 1B1 contributes to the development of hypertension, as well as AAAs, in male mice. We also found that a cytochrome P450 1B1-generated metabolite of testosterone, 6β-hydroxytestosterone (6β-OHT), contributes to Ang II-induced hypertension and associated cardiovascular and renal pathogenesis in male mice. Read More

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VPS4B deficiency causes early embryonic lethality and induces signal transduction disorders of cell endocytosis.

Genesis 2021 Apr 7;59(4):e23415. Epub 2021 Mar 7.

Department of Medical Genetics, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China.

VPS4B (vacuolar protein sorting 4B), a member of the ATPase associated with diverse cellular activities (AAA) protein family, is a component of the endosomal sorting complexes required for transport machinery which regulates the internalization and lysosomal degradation of membrane proteins. We previously reported that VPS4B is one of the pathogenic genes related to dentin dysplasia type I, although its function was largely unknown. To investigate the role of VPS4B in tooth development, we deleted the Vps4b gene in mice. Read More

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MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm.

Redox Biol 2021 May 20;41:101903. Epub 2021 Feb 20.

Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY, USA; Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA. Electronic address:

Abdominal aortic aneurysm (AAA) is a catastrophic disease with little effective therapy. Myocardin related transcription factor A (MRTFA, MKL1) is a multifaceted transcription factor, regulating diverse biological processes. However, a detailed understanding of the mechanistic role of MKL1 in AAA has yet to be elucidated. Read More

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Deletion of Von Willebrand A Domain Containing Protein (VWA8) raises activity of mitochondrial electron transport chain complexes in hepatocytes.

Biochem Biophys Rep 2021 Jul 15;26:100928. Epub 2021 Feb 15.

Department of Medicine, Division of Endocrinology, USA.

VWA8 (Von Willebrand A Domain Containing Protein 8) is a AAA+ ATPase that is localized to the mitochondrial matrix and is widely expressed in highly energetic tissues. Originally found to be higher in abundance in livers of mice fed a high fat diet, deletion of the VWA8 gene in differentiated mouse AML12 hepatocytes unexpectedly produced a phenotype of higher mitochondrial and nonmitochondrial oxidative metabolism, higher ROS (reactive oxygen species) production mainly from NADPH oxidases, and increased HNF4a expression. The purposes of this study were first, to determine whether higher mitochondrial oxidative capacity in VWA8 null hepatocytes is the product of higher capacity in all aspects of the electron transport chain and oxidative phosphorylation, and second, the density of cristae in mitochondria and mitochondrial content was measured to determine if higher mitochondrial oxidative capacity is accompanied by greater cristae area and mitochondrial abundance. Read More

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MicroRNA-194 acts as a suppressor during abdominal aortic aneurysm via inhibition of KDM3A-mediated BNIP3.

Life Sci 2021 Mar 1;277:119309. Epub 2021 Mar 1.

Department of Vascular Surgery, The First Hospital of Jilin University, Changchun 130021, PR China. Electronic address:

Aims: Abdominal aortic aneurysm (AAA) is a serious disorder with a high disability rates and mortality rates. Accumulating evidence has identified the vital functions of microRNAs (miRNAs) in the treatment of AAA. Hence, this study is aimed at exploring the modulatory role of miR-194 in the development of AAA. Read More

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miRNAs regulating the expressions of NTF3, GNG2 and ITGA7 are involved in the pathogenesis of abdominal aortic aneurysm in mice.

Gen Physiol Biophys 2021 Jan;40(1):1-16

Department of Vascular Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease, but effective treatment strategies remain lacking. The objective of this study was to screen underlying therapeutic targets by investigating the molecular mechanisms of AAA using mouse models. The mRNA (GSE109639) and miRNA (GSE51229 and GSE54943) expression profiles of mouse AAA models were downloaded from Gene Expression Omnibus database. Read More

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January 2021

Relieves Depressive-Like Behavior through the Restoration of Glial Loss in the Prefrontal Cortex.

Evid Based Complement Alternat Med 2021 12;2021:8888841. Epub 2021 Feb 12.

Department of Clinical Korean Medicine, Graduate School, Kyung Hee University, Seoul 02447, Republic of Korea.

, which is a halophyte and grows widely in Asian-Pacific regions, has been used for the treatment of digestive disorders in traditional oriental medicine. This study examined the potential antidepressant effect of in an astroglial degeneration model of depression, which was established based on the postmortem study of depressive patients' brain presenting diminished astrocytes in the prefrontal cortex. C57BL/6 male mice were exposed to glial ablation in the prefrontal cortex by the administration of the gliotoxin, L-alpha-aminoadipic acid (L-AAA) to induce depression. Read More

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February 2021

Inhibition of CXCR2 alleviates the development of abdominal aortic aneurysm in Apo E-/- mice.

Acta Cir Bras 2021 15;36(1):e360105. Epub 2021 Feb 15.

PhD. Weifang People's Hospital - Department of Vascular Surgery - Weifang, Shandong, China.

Purpose: To investigate the relationship between atherosclerotic abdominal aortic aneurysm (AAA) and CXC chemokine receptor type 2 (CXCR2).

Methods: Mouse AAA model was established by embedding angiotensin-II pump (1000 ng/kg/min) in ApoE-/- mice. Mice were received SB225002, a selective CXCR2 antagonist, for treatment. Read More

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February 2021

Kallikrein-1 Blockade Inhibits Aortic Expansion in a Mouse Model and Reduces Prostaglandin E2 Secretion From Human Aortic Aneurysm Explants.

J Am Heart Assoc 2021 Feb 18;10(5):e019372. Epub 2021 Feb 18.

Queensland Research Centre for Peripheral Vascular Disease College of Medicine and Dentistry James Cook University Townsville Australia.

Background Abdominal aortic aneurysm (AAA) is an important cause of mortality in older adults. The kinin B2 receptor agonist, bradykinin, has been implicated in AAA pathogenesis through promoting inflammation. Bradykinin is generated from high- and low-molecular-weight kininogen by the serine protease kallikrein-1. Read More

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February 2021

Targeted deletion of Ruvbl1 results in severe defects of epidermal development and perinatal mortality.

Mol Cell Pediatr 2021 Feb 12;8(1). Epub 2021 Feb 12.

Department of Pediatrics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.

Epidermal development is a complex process of regulated cellular proliferation, differentiation, and tightly controlled cell death involving multiple cellular signaling networks. Here, we report a first description linking the AAA+ (ATPases associated with various cellular activities) superfamily protein Ruvbl1 to mammalian epidermal development. Keratinocyte-specific Ruvbl1 knockout mice (Ruvbl1K14:Cre) show a severe phenotype including dramatic structural epidermal defects resulting in the loss of the functional skin barrier and perinatal death. Read More

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February 2021

AAV- protects against vision loss in an inducible retinitis pigmentosa mouse model.

Mol Ther Methods Clin Dev 2021 Mar 25;20:423-441. Epub 2020 Dec 25.

Department of Ophthalmology, Leiden University Medical Center (LUMC), 2333 ZC Leiden, the Netherlands.

Loss of Crumbs homolog 1 (CRB1) or CRB2 proteins in Müller cells or photoreceptors in the mouse retina results in a CRB dose-dependent retinal phenotype. In this study, we present a novel Müller cell-specific retinitis pigmentosa mouse model (complete loss of CRB1 and reduced levels of CRB2 specifically in Müller cells). The double mutant mice showed deficits in electroretinography, optokinetic head tracking, and retinal morphology. Read More

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Histone citrullination as a novel biomarker and target to inhibit progression of abdominal aortic aneurysms.

Transl Res 2021 Feb 9. Epub 2021 Feb 9.

Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University Munich, Munich, Germany; Molecular Vascular Medicine Group, Centre for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.

Neutrophil extracellular traps (NETs) have been implicated in the pathogenesis of abdominal aortic aneurysms (AAAs). This study has addressed the notion that NET components might serve as AAA biomarkers or novel targets of AAA therapy. Thus, parameters of neutrophil activation and NET formation were measured in plasma. Read More

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February 2021

GSK2593074A blocks progression of existing abdominal aortic dilation.

JVS Vasc Sci 2020 28;1:123-135. Epub 2020 Jul 28.

Department of Surgery, School of Medicine and Public Health, University of Wisconsin-Madison.

Objective: Receptor interacting proteins kinase 1 and 3 (RIPK1 and RIPK3) have been shown to play essential roles in the pathogenesis of abdominal aortic aneurysms (AAAs) by mediating necroptosis and inflammation. We previously discovered a small molecular inhibitor GSK2593074A (GSK'074) that binds to both RIPK1 and RIPK3 with high affinity and prevents AAA formation in mice. In this study, we evaluated whether GSK'074 can attenuate progression of existing AAA in the calcium phosphate model. Read More

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Inhibition of Notch1-mediated inflammation by intermedin protects against abdominal aortic aneurysm via PI3K/Akt signaling pathway.

Aging (Albany NY) 2021 02 1;13(4):5164-5184. Epub 2021 Feb 1.

Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing 100083, China.

The Notch1-mediated inflammatory response participates in the development of abdominal aortic aneurysm (AAA). The vascular endogenous bioactive peptide intermedin (IMD) plays an important role in maintaining vascular homeostasis. However, whether IMD inhibits AAA by inhibiting Notch1-mediated inflammation is unclear. Read More

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February 2021

Cartilage oligomeric matrix protein is an endogenous β-arrestin-2-selective allosteric modulator of AT1 receptor counteracting vascular injury.

Cell Res 2021 Jan 28. Epub 2021 Jan 28.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University; Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing, 100191, China.

Compelling evidence has revealed that biased activation of G protein-coupled receptor (GPCR) signaling, including angiotensin II (AngII) receptor type 1 (AT1) signaling, plays pivotal roles in vascular homeostasis and injury, but whether a clinically relevant endogenous biased antagonism of AT1 signaling exists under physiological and pathophysiological conditions has not been clearly elucidated. Here, we show that an extracellular matrix protein, cartilage oligomeric matrix protein (COMP), acts as an endogenous allosteric biased modulator of the AT1 receptor and its deficiency is clinically associated with abdominal aortic aneurysm (AAA) development. COMP directly interacts with the extracellular N-terminus of the AT1 via its EGF domain and inhibits AT1-β-arrestin-2 signaling, but not Gq or Gi signaling, in a selective manner through allosteric regulation of AT1 intracellular conformational states. Read More

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January 2021

Single-Cell RNA Sequencing Reveals Heterogeneity of Vascular Cells in Early Stage Murine Abdominal Aortic Aneurysm-Brief Report.

Arterioscler Thromb Vasc Biol 2021 03 21;41(3):1158-1166. Epub 2021 Jan 21.

Department of Surgery (H.Y., T.Z., A.S., E.D., B.L.), School of Medicine and Public Health, University of Wisconsin-Madison, Madison.

Objective: Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by smooth muscle cell depletion, ECM (extracellular matrix) degradation, and infiltration of immune cells. The cellular and molecular profiles that govern the heterogeneity of the AAA aorta are yet to be elucidated. Approach and Results: We performed single-cell RNA sequencing on mouse AAA tissues. Read More

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Interleukin 12p40 Deficiency Promotes Abdominal Aortic Aneurysm by Activating CCN2/MMP2 Pathways.

J Am Heart Assoc 2021 Feb 20;10(3):e017633. Epub 2021 Jan 20.

Department of Cardiovascular Medicine University of Missouri Columbia MO.

Background Development of abdominal aortic aneurysm (AAA) is associated with proinflammatory cytokines including interleukin-12 (IL12). Deficiency of interleukin 12p40 (IL12p40) increases localized fibrotic events by promoting TGFβ2 (transforming growth factor β)-dependent anti-inflammatory response. Here, we determined whether IL12p40 deficiency in apolipoprotein E mice attenuates the development of AAA by antagonizing proinflammatory response. Read More

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February 2021

A Dual Role of Heme Oxygenase-1 in Angiotensin II-Induced Abdominal Aortic Aneurysm in the Normolipidemic Mice.

Cells 2021 01 15;10(1). Epub 2021 Jan 15.

Department of Medical Biotechnology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-392 Krakow, Poland.

Abdominal aortic aneurysm (AAA) bears a high risk of rupture and sudden death of the patient. The pathogenic mechanisms of AAA remain elusive, and surgical intervention represents the only treatment option. Heme oxygenase-1 (HO-1), a heme degrading enzyme, is induced in AAA, both in mice and humans. Read More

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January 2021

Nanoparticle-Mediated Delivery of Pitavastatin to Monocytes/Macrophages Inhibits Angiotensin II-Induced Abdominal Aortic Aneurysm Formation in Apoe Mice.

J Atheroscler Thromb 2021 Jan 15. Epub 2021 Jan 15.

The Department of Cardiovascular Research, Development, and Translational Medicine, Center for Disruptive Cardiovascular Innovation, Kyushu University.

Aim: Abdominal aortic aneurysm (AAA) is a lethal and multifactorial disease. To prevent a rupture and dissection of enlarged AAA, prophylactic surgery and stenting are currently available. There are, however, no medical therapies preventing these complications of AAA. Read More

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January 2021