scholarly journals Galectin-3 Modulates Macrophage Activation and Contributes Smooth Muscle Cells Apoptosis in Abdominal Aortic Aneurysm Pathogenesis

2020 ◽  
Vol 21 (21) ◽  
pp. 8257
Author(s):  
Hsin-Ying Lu ◽  
Chun-Ming Shih ◽  
Chun-Yang Huang ◽  
Alexander T. H. Wu ◽  
Tsai-Mu Cheng ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Messenger Rna ◽  
Macrophage Activation ◽  
In Vitro Study ◽  
Abdominal Aortic ◽  
Galectin 3 ◽  
Apoe Knockout Mice

Galectin-3 (Gal-3) is a 26-kDa lectin that regulates many aspects of inflammatory cell behavior. We assessed the hypothesis that increased levels of Gal-3 contribute to abdominal aortic aneurysm (AAA) progression by enhancing monocyte chemoattraction through macrophage activation. We analyzed the plasma levels of Gal-3 in 76 patients with AAA (AAA group) and 97 controls (CTL group) as well as in angiotensin II (Ang-II)-infused ApoE knockout mice. Additionally, conditioned media (CM) were used to polarize THP-1 monocyte to M1 macrophages with or without Gal-3 inhibition through small interfering RNA targeted deletion to investigate whether Gal-3 inhibition could attenuate macrophage-induced inflammation and smooth muscle cell (SMC) apoptosis. Our results showed a markedly increased expression of Gal-3 in the plasma and aorta in the AAA patients and experimental mice compared with the CTL group. An in vitro study demonstrated that the M1 cells exhibited increased Gal-3 expression. Gal-3 inhibition markedly decreased the quantity of macrophage-induced inflammatory regulators, including IL-8, TNF-α, and IL-1β, as well as messenger RNA expression and MMP-9 activity. Moreover, Gal-3-deficient CM weakened SMC apoptosis through Fas activation. These findings prove that Gal-3 may contribute to AAA progression by the activation of inflammatory macrophages, thereby promoting SMC apoptosis.

scholarly journals Genetic and Epigenetic Mechanisms Underlying Vascular Smooth Muscle Cell Phenotypic Modulation in Abdominal Aortic Aneurysm

2020 ◽  
Vol 21 (17) ◽  
pp. 6334
Author(s):  
Rijan Gurung ◽  
Andrew Mark Choong ◽  
Chin Cheng Woo ◽  
Roger Foo ◽  
Vitaly Sorokin
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Aortic Wall ◽  
Epigenetic Mechanisms ◽  
Phenotypic Modulation ◽  
Abdominal Aortic

Abdominal aortic aneurysm (AAA) refers to the localized dilatation of the infra-renal aorta, in which the diameter exceeds 3.0 cm. Loss of vascular smooth muscle cells, degradation of the extracellular matrix (ECM), vascular inflammation, and oxidative stress are hallmarks of AAA pathogenesis and contribute to the progressive thinning of the media and adventitia of the aortic wall. With increasing AAA diameter, and left untreated, aortic rupture ensues with high mortality. Collective evidence of recent genetic and epigenetic studies has shown that phenotypic modulation of smooth muscle cells (SMCs) towards dedifferentiation and proliferative state, which associate with the ECM remodeling of the vascular wall and accompanied with increased cell senescence and inflammation, is seen in in vitro and in vivo models of the disease. This review critically analyses existing publications on the genetic and epigenetic mechanisms implicated in the complex role of SMCs within the aortic wall in AAA formation and reflects the importance of SMCs plasticity in AAA formation. Although evidence from the wide variety of mouse models is convincing, how this knowledge is applied to human biology needs to be addressed urgently leveraging modern in vitro and in vivo experimental technology.

Abstract 106: Receptor Interacting Kinase 1 Contributes to Pathogenesis of Abdominal Aortic Aneurysm by Causing Smooth Muscle Cell Necroptosis as Well as Inflammation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Noel M Phan ◽  
Ting Zhou ◽  
Qiwei Wang ◽  
Kartik Gupta ◽  
Conner Feldman ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Aortic Rupture ◽  
Treated Group ◽  
Aortic Disease ◽  
Interacting Protein ◽  
Aneurysm Formation ◽  
Abdominal Aortic

Objectives: Abdominal aortic aneurysm (AAA), the progressive weakening and dilatation most commonly occurred in the infrarenal segment of aorta, is a common aortic disease associated with high lethality. Currently, there is no approved pharmacological treatment to effectively slow aneurysm growth or prevent rupture. We have recently demonstrated that inhibition of receptor interacting protein kinase 1 (RIP1), a critical mediator of necroptosis and apoptosis, attenuates aneurysm pathogenesis in a mouse elastase AAA model. Here, we tested whether RIP1 is also required for aneurysm formation in hypercholesterolemia mice stressed with Angiotensin II (AngII). Methods: Apolipoprotein E-deficient mice were infused with 1000 ng/kg/min of AngII for 28 days. The RIP1 inhibitor Necrostatin-1s (Nec-1s, 1.6 mg/kg/day) was administered via daily intraperitoneal (IP) injection. An aneurysm is defined as aortic expansion in the suprarenal ≥50% over infrarenal diameter. Results: The incidence of aneurysm formation was significantly lower in Nec-1s treated group compared to the DMSO group (33.35 vs 90.5%). Additionally, Nec-1s reduced aortic expansion (DMSO: 55.40±13.80%, Nec-1s: 121.1±16.44%, p<0.05 unpaired student’s t test). The number of mice that died prior to 28 days (due to aortic rupture) were comparable between DMSO and Nec-1 groups. Histological analysis showed preserved elastin fibers in aortae from Nec-1s treatment vs DMSO treatment. Immunohistochemical and immunofluorescence staining revealed that Nec-1s decreased the abundance of CD68+ cells as well as CD3+ T-cells but relative higher number of CD206 positive M2 macrophages in the aneurysm prone aortae. In vitro, Nec-1s attenuated smooth muscle necroptosis but stimulated biosynthesis of elastin. Furthermore, Nec-1s inhibited chemotaxis of monocytes/macrophages. Conclusions: Our data demonstrate that RIP1 contributes to aneurysm pathophysiology through regulation of cell death and inflammation infiltration. Being a small chemical molecule that is highly selective for RIP1, Necrostatin-1s may serve as a suitable drug treatment for AAAs.

scholarly journals Histochemical and immunohistochemical analysis of ruptured atherosclerotic abdominal aortic aneurysm wall

2010 ◽  
Vol 67 (12) ◽  
pp. 959-964 ◽  
Author(s):  
Irena Tanaskovic ◽  
Aleksandra Mladenovic-Mihailovic ◽  
Slavica Usaj-Knezevic ◽  
Vesna Stankovic ◽  
Aleksandar Aleksic ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Periodic Acid ◽  
Muscle Cells ◽  
Foam Cells ◽  
Abdominal Aortic ◽  
S 100 ◽  
The Media

Background/Aim. The main complication of the atherosclerotic abdominal aortic aneurism (AAA) is her rupture that begins with lesion in intima and rupture. The purpose of this work was to determine immunocytochemical and morphofunctional characteristics of the cells in aortic wall in ruptured atherosclerotic abdominal aortic aneurysm. Method. During the course of this study, 20 samples of atherosclerotic AAA were analyzed, all of them obtained during authopsy. The samples were fixed in 4% formalin and embedded in paraffin. Sections of 5 ?m thickness were stained histochemically (of Heidenhain azan stain and Periodic acid Schiff - PAS stain) and immunocytochemically using a DAKO LSAB+/HRP technique to identify ?-smooth muscle actin (?-SMA), vimentin, myosin heavy chains (MHC), desmin, S-100 protein, CD45 and CD68 (DAKO specification). Results. The results of our study showed that ruptured atherosclerotic AAA is characterized by a complete absence of endothelial cells, the disruption of basal membrane and internal elastic lamina, as well as a presence of the remains of hypocellular complicated atherosclerotic lesion in intima. On the plaque margins, as well as in the media, smooth muscle cells (SMCs) are present, which express a ?-SMA and vimentin (but without MHC or desmin expression), as well as leukocyte infiltration, and a large number of foam cells. Some of the foam cells show a CD68-immunoreactivity, while the others show vimentin- and S-100 protein-immunoreactivity. Media is thinned out with a disorganized elastic lamellas, while adventitia is characterized by inflammatory inflitrate (infection). Conclusion. Rupture of aneurysm occurs from the primary intimal disruption, which spreads into thinned out media and adventitia. Rupture is caused by unstable atherom, hypocellularity, loss of contractile characteristics of smooth muscle cells in intima and media, neovascularization of the media, as well as by the activity of the macrophages in the lesion.

scholarly journals Identification of Novel Long Noncoding RNAs and Their Role in Abdominal Aortic Aneurysm

2020 ◽  
Vol 2020 ◽  
pp. 1-22
Author(s):  
Abulaihaiti Maitiseyiti ◽  
Hongbo Ci ◽  
Qingbo Fang ◽  
Sheng Guan ◽  
Alimujiang Shawuti ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Functional Enrichment ◽  
Pcr Analysis ◽  
Control Group ◽  
Abdominal Aortic

Objective. Long noncoding RNAs (lncRNAs) have emerged as critical molecular regulators in various diseases. However, the potential regulatory role of lncRNAs in the pathogenesis of abdominal aortic aneurysm (AAA) remains elusive. The aim of this study was to identify crucial lncRNAs associated with human AAA by comparing the lncRNA and mRNA expression profiles of patients with AAA with those of control individuals. Materials and Methods. The expression profiles of lncRNAs and mRNAs were analyzed in five dilated aortic samples from AAA patients and three normal aortic samples from control individuals using microarray technology. Functional annotation of the screened lncRNAs based on the differentially expressed genes was performed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Results. Microarray results revealed 2046 lncRNAs and 1363 mRNAs. Functional enrichment analysis showed that the mRNAs significantly associated with AAA were enriched in the NOD-like receptor (NLR) and nuclear factor kappa-B (NF-κB) signaling pathways and in cell adhesion molecules (CAMs), which are closely associated with pathophysiological changes in AAA. The lncRNAs identified using microarray analysis were further validated using quantitative real-time polymerase chain reaction (qRT-PCR) analysis with 12 versus 11 aortic samples. Finally, three key lncRNAs (ENST00000566954, ENST00000580897, and T181556) were confirmed using strict validation. A coding-noncoding coexpression (CNC) network and a competing endogenous RNA (ceRNA) network were constructed to determine the interaction among the lncRNAs, microRNAs, and mRNAs based on the confirmed lncRNAs. Conclusions. Our microarray profiling analysis and validation of significantly expressed lncRNAs between patients with AAA and control group individuals may provide new diagnostic biomarkers for AAA. The underlying regulatory mechanisms of the confirmed lncRNAs in AAA pathogenesis need to be determined using in vitro and in vivo experiments.

scholarly journals SM22α Loss Contributes to Apoptosis of Vascular Smooth Muscle Cells via Macrophage-Derived circRasGEF1B

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Pin Lv ◽  
Ya-Juan Yin ◽  
Peng Kong ◽  
Li Cao ◽  
Hao Xi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Vascular Smooth Muscle ◽  
Inflammatory Cell ◽  
Activated Macrophages ◽  
Abdominal Aortic ◽  
Specific Manner ◽  
Higher Sensitivity

Vascular smooth muscle cell (VSMC) apoptosis is a major defining feature of abdominal aortic aneurysm (AAA) and mainly caused by inflammatory cell infiltration. Smooth muscle (SM) 22α prevents AAA formation through suppressing NF-κB activation. However, the role of SM22α in VSMC apoptosis is controversial. Here, we identified that SM22α loss contributed to apoptosis of VSMCs via activation of macrophages. Firstly, deficiency of SM22α enhanced the interaction of VSMCs with macrophages. Macrophages were retained and activated by Sm22α-/- VSMCs via upregulating VCAM-1 expression. The ratio of apoptosis was increased by 1.62-fold in VSMCs treated with the conditional media (CM) from activated RAW264.7 cells, compared to that of the control CM ( P < 0.01 ), and apoptosis of Sm22α-/- VSMCs was higher than that of WT VSMCs ( P < 0.001 ). Next, circRasGEF1B from activated macrophages was delivered into VSMCs promoting ZFP36 expression via stabilization of ZFP36 mRNA. Importantly, circRasGEF1B, as a scaffold, guided ZFP36 to preferentially bind to and decay Bcl-2 mRNA in a sequence-specific manner and triggered apoptosis of VSMCs, especially in Sm22α-/- VSMCs. These findings reveal a novel mechanism by which the circRasGEF1B-ZFP36 axis mediates macrophage-induced VSMC apoptosis via decay of Bcl-2 mRNA, whereas Sm22α-/- VSMCs have a higher sensitivity to apoptosis.

Peri-Adventitial Delivery of Smooth Muscle Cells in Porous Collagen Scaffolds for Treatment of Experimental Abdominal Aortic Aneurysm

2021 ◽  
Author(s):  
Joscha Mulorz ◽  
Mahdis Shayan ◽  
Caroline Hu ◽  
Cynthia Alcazar ◽  
Alex H.P Chan ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Vessel Wall ◽  
Muscle Cells ◽  
Collagen Scaffolds ◽  
Abdominal Aortic ◽  
Direct Delivery

Abdominal aortic aneurysm (AAA) is associated with the loss of vascular smooth muscle cells (SMCs) within the vessel wall. Direct delivery of therapeutic cells is challenging due to impaired mechanical...

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