scholarly journals Levels of Circulating MMCN-151, a Degradation Product of Mimecan, Reflect Pathological Extracellular Matrix Remodeling in Apolipoprotein E Knockout Mice

2011 ◽  
Vol 6 ◽  
pp. BMI.S7777 ◽  
Author(s):  
N. Barascuk ◽  
E. Vassiliadis ◽  
Q. Zheng ◽  
Y. Wang ◽  
W. Wang ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Apolipoprotein E ◽  
Enzyme Linked Immunosorbent Assay ◽  
Matrix Remodeling ◽  
Limit Of Quantification ◽  
Ecm Remodeling ◽  
Apolipoprotein E Knockout Mice ◽  
Significant Difference ◽  
Apoe Ko Mice ◽  
Apoe Ko

Aim Arterial extracellular matrix (ECM) remodeling by matrix metalloproteinases (MMPs) is one of the major hallmarks of atherosclerosis. Mimecan, also known as osteoglycin has been implicated in the integrity of the ECM. This study assessed the validity of an enzyme-linked immunosorbent assay (ELISA) developed to measure a specific MMP12-derived fragment of mimecan, MMCN-151, in apolipoprotein-E knockout (ApoE-KO) mice. Methods and Results A mouse monoclonal antibody raised against MMCN-151 was used to develop a competitive ELISA. The assay was validated using samples from 20 ApoE-KO and 20 wild type [C57 BL/6] male mice fed a normal or high-fat diet (HFD) for up to 20 weeks. The technical reliability of the assay was established with intra-assay variability <2% and inter-assay variability < 10%. The lowest limit of quantification of MMCN-151 was 0.5 ng/ml. ApoE-KO mice fed a HFD for 20 weeks had four-fold increased circulating levels of MMCN-151 compared to baseline, whereas MMCN-151 levels in control mice on HFD increased two-fold compared with baseline. After 10 weeks of a HFD, a significant difference in MMCN-151 levels was observed between ApoE-KO and control mice ( P = 0.005) and became more significant at 20 weeks ( P = 0.002). Conclusions The newly developed assay is a reliable detector of MMCN-151 levels which ultimately may be useful indicators of arterial remodeling in patients affected by atherosclerotic disease.

Granzyme B contributes to extracellular matrix remodeling and skin aging in apolipoprotein E knockout mice

2011 ◽  
Vol 46 (6) ◽  
pp. 489-499 ◽  
Author(s):  
Paul R. Hiebert ◽  
Wendy A. Boivin ◽  
Thomas Abraham ◽  
Sara Pazooki ◽  
Hongyan Zhao ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Apolipoprotein E ◽  
Knockout Mice ◽  
Granzyme B ◽  
Skin Aging ◽  
Extracellular Matrix Remodeling ◽  
Matrix Remodeling ◽  
Apolipoprotein E Knockout Mice

Xenogenic macrophage immunization reduces atherosclerosis in apolipoprotein E knockout mice

2007 ◽  
Vol 293 (3) ◽  
pp. C865-C873 ◽  
Author(s):  
Tomoya Yamashita ◽  
Seinosuke Kawashima ◽  
Tetsuaki Hirase ◽  
Masakazu Shinohara ◽  
Tomofumi Takaya ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Plasma Lipid ◽  
Chronic Inflammatory Disease ◽  
Apolipoprotein E Knockout Mice ◽  
Apoe Ko Mice ◽  
Apoe Ko

Atherosclerosis is a complex chronic inflammatory disease in which macrophages play a critical role, and the intervention of the inflammatory process in atherogenesis could be a therapeutic strategy. In this study, we investigated the efficacy of xenogenic macrophage immunization on the atherosclerotic lesion formation in a model of murine atherosclerosis. Apolipoprotein E knockout (apoE-KO) mice were repeatedly immunized with formaldehyde-fixed cultured human macrophages (phorbol ester-stimulated THP-1 cells), using human serum albumin as a control protein or HepG2 cells as human control cells, once a week for four consecutive weeks. The vehicle phosphate-buffered saline was injected in the nonimmunized controls. THP-1 immunization induced antibodies that are immunoreactive with mouse macrophages. Although the plasma lipid levels were unchanged by the immunization, the atherosclerotic lesion area in the aortic root was significantly reduced by >50% in 16-wk-old THP-1-immunized apoE-KO mice compared with that in control mice. THP-1 immunization reduced in vivo macrophage infiltration, reduced in vitro macrophage adhesion, and changed cytokine production by macrophages to the antiatherogenic phenotype. Xenogenic macrophage immunization protects against the development of atherosclerosis in apoE-KO mice by modulating macrophage function in which antibodies induced by the immunization are likely to be involved. This method is a novel and potentially useful cell-mediated immune therapeutic technique against atherosclerosis.

scholarly journals Prediction of the Network Pharmacology-Based Mechanism for Attenuation of Atherosclerosis in Apolipoprotein E Knockout Mice by Panax notoginseng Saponins

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Linzi Long ◽  
Zikai Yu ◽  
Hua Qu ◽  
Ning Wang ◽  
Ming Guo ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Signaling Pathway ◽  
Fluid Shear Stress ◽  
Atherosclerotic Lesion ◽  
Panax Notoginseng ◽  
Network Pharmacology ◽  
Chemical Components ◽  
Apolipoprotein E Knockout Mice ◽  
Apoe Ko Mice ◽  
Apoe Ko

This study investigated whether Panax notoginseng saponins (PNS) reduced atherosclerotic lesion formation in apolipoprotein E knockout (ApoE-KO) mice and illustrated the potential mechanism for a network pharmacology approach. Pharmacodynamics studies on ApoE-KO mice with atherosclerosis (AS) showed that PNS generated an obvious anti-AS action. Then, we explored the possible mechanisms underlying its anti-AS effect using the network pharmacology approach. The main chemical components and their targets of PNS were collected from TCMSP public database and SymMap. The STRING v11.0 was used to establish the protein-protein interactions of PNS. Furthermore, the Gene Ontology (GO) function and KEGG pathways were analyzed using STRING to investigate the possible mechanisms involved in the anti-AS effect of PNS. The predicted results showed that 27 potential targets regulated by DSLHG were related to AS, including ACTA2, AKT1, BCL2, and BDNF. Mechanistically, the anti-AS effect of PNS was exerted by interfering with multiple signaling pathways, such as AGE-RAGE signaling pathway, fluid shear stress and atherosclerosis, and TNF signaling pathway. Network analysis showed that PNS could generate the anti-AS action by affecting multiple targets and multiple pathways and provides a novel basis to clarify the mechanisms of anti-AS of PNS.

scholarly journals Engineering cardiac microphysiological systems to model pathological extracellular matrix remodeling

2018 ◽  
Vol 315 (4) ◽  
pp. H771-H789 ◽  
Author(s):  
Nethika R. Ariyasinghe ◽  
Davi M. Lyra-Leite ◽  
Megan L. McCain
Keyword(s):  
Cardiovascular Disease ◽  
Extracellular Matrix ◽  
Myocardial Function ◽  
Myocardial Cell ◽  
Three Dimensions ◽  
Model Systems ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Microphysiological Systems

Many cardiovascular diseases are associated with pathological remodeling of the extracellular matrix (ECM) in the myocardium. ECM remodeling is a complex, multifactorial process that often contributes to declines in myocardial function and progression toward heart failure. However, the direct effects of the many forms of ECM remodeling on myocardial cell and tissue function remain elusive, in part because conventional model systems used to investigate these relationships lack robust experimental control over the ECM. To address these shortcomings, microphysiological systems are now being developed and implemented to establish direct relationships between distinct features in the ECM and myocardial function with unprecedented control and resolution in vitro. In this review, we will first highlight the most prominent characteristics of ECM remodeling in cardiovascular disease and describe how these features can be mimicked with synthetic and natural biomaterials that offer independent control over multiple ECM-related parameters, such as rigidity and composition. We will then detail innovative microfabrication techniques that enable precise regulation of cellular architecture in two and three dimensions. We will also describe new approaches for quantifying multiple aspects of myocardial function in vitro, such as contractility, action potential propagation, and metabolism. Together, these collective technologies implemented as cardiac microphysiological systems will continue to uncover important relationships between pathological ECM remodeling and myocardial cell and tissue function, leading to new fundamental insights into cardiovascular disease, improved human disease models, and novel therapeutic approaches.

scholarly journals Bone Mesenchymal Stem Cells Promote Extracellular Matrix Remodeling of Degenerated Nucleus Pulposus Cells via the miR-101-3p/EIF4G2 Axis

2021 ◽  
Vol 9 ◽  
Author(s):  
Zeng Wang ◽  
Xiaolin Ding ◽  
Feifei Cao ◽  
Xishan Zhang ◽  
Jingguo Wu
Keyword(s):  
Extracellular Matrix ◽  
Nucleus Pulposus ◽  
Quantitative Polymerase Chain Reaction ◽  
Matrix Remodeling ◽  
Nucleus Pulposus Cells ◽  
Promoting Effect ◽  
Bone Mesenchymal Stem Cells ◽  
Ecm Remodeling ◽  
Lumbar Vertebral Fracture ◽  
Related Proteins

The etiology of lumbocrural pain is tightly concerned with intervertebral disk degeneration (IDD). Bone mesenchymal stem cell (BMSC)-based therapy bears potentials for IDD treatment. The properties of microRNA (miRNA)-modified BMSCs may be altered. This study investigated the role and mechanism of BMSCs promoting extracellular matrix (ECM) remodeling of degenerated nucleus pulposus cells (NPCs) via the miR-101-3p/EIF4G2 axis. NPCs were collected from patients with IDD and lumbar vertebral fracture (LVF). The expressions of miR-101-3p and ECM-related proteins, Collagen-I (Col-I) and Collagen-II (Col-II), were detected using the reverse transcription-quantitative polymerase chain reaction. The expressions of Col-I and Col-II, major non-collagenous component Aggrecan, and major catabolic factor Matrix metalloproteinase-13 (MMP-13) were detected using Western blotting. BMSCs were cocultured with degenerated NPCs from patients with IDD. Viability and apoptosis of NPCs were measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry. After the degenerated NPCs were transfected with the miR-101-3p inhibitor, the expressions of ECM-related proteins, cell viability, and apoptosis were detected. The targeting relationship between miR-101-3p and EIF4G2 was verified. Functional rescue experiments verified the effects of miR-101-3p and EIF4G2 on ECM remodeling of NPCs. Compared with the NPCs of patients with LVF, the degenerated NPCs of patients with IDD showed downregulated miR-101-3p, Col-II, and Aggrecan expressions and upregulated MMP-13 and Col-I expressions. BMSCs increased the expressions of miR-101-3p, Aggrecan, and Col-II, and decreased the expressions of MMP-13 and Col-I in degenerated NPCs. BMSCs enhanced NPC viability and repressed apoptosis. Downregulation of miR-101-3p suppressed the promoting effect of BMSCs on ECM remodeling. miR-101-3p targeted EIF4G2. Downregulation of EIF4G2 reversed the inhibiting effect of the miR-101-3p inhibitor on ECM remodeling. In conclusion, BMSCs increased the miR-101-3p expression in degenerated NPCs to target EIF4G2, thus promoting the ECM remodeling of NPCs.

4.P.27 Identification and localization of interleukin-6 (IL-6) mRNA and secreted protein in vascular lesions of apolipoprotein E knock-out (ApoE-KO) mice

1997 ◽  
Vol 134 (1-2) ◽  
pp. 301
Author(s):  
D.A. Sukovich ◽  
K. Kauser ◽  
F.D. Shirley ◽  
V. DelVecchio ◽  
M. Halks-Miller ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Interleukin 6 ◽  
Vascular Lesions ◽  
Secreted Protein ◽  
Knock Out ◽  
Apoe Ko Mice ◽  
Apoe Ko

scholarly journals Peri-implantitis and extracellular matrix antibodies: A case–control study

2017 ◽  
Vol 11 (03) ◽  
pp. 340-344 ◽  
Author(s):  
Piero Papi ◽  
Stefano Di Carlo ◽  
Daniele Rosella ◽  
Francesca De Angelis ◽  
Mario Capogreco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Case Control Study ◽  
Test Group ◽  
Case Control ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Fisher Exact Test ◽  
Type I ◽  
Significant Difference ◽  
Control Study

ABSTRACT Objective: The aim of this case–control study was to compare patients with a healthy peri-implant environment and patients affected by peri-implantitis, evaluating the occurrence of antibodies to extracellular matrix (ECM) molecules. The authors hypothesized the presence of ECM autoantibodies in serum of peri-implantitis patients. Materials and Methods: Patients were divided into two groups: one with dental implants with a diagnosis of peri-implantitis and one control group with implants classified as being “healthy.” Enzyme-linked immunosorbent assay was performed on patients' sera to detect human antibodies to type I, III, IV, and V collagens, laminin, and fibronectin. Fisher exact test was performed to evaluate statistical association, with a significant P < 0.05. Results: Forty-two patients were enrolled in this study, 27 females (64.28%) and 15 males (35.72%) with a mean age of 53 ± 29.69 years (age range 32–74). The presence of antibodies to CIII was recorded in 6/21 (28.57%) patients of test group, compared to just 2/21 (9.52%) for the control group, showing a statistically significant difference (P < 0.05). Other antibodies tested were found to be not statistically significant or absent. Conclusions: Within the limitations of this study, it can be concluded that further studies, with larger sample and different design, are necessary to address the research purpose, evaluating possible associations between anti-ECM antibodies and peri-implantitis.

scholarly journals Aryl Hydrocarbon Receptor Activation by TCDD Modulates Expression of Extracellular Matrix Remodeling Genes during Experimental Liver Fibrosis

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Cheri L. Lamb ◽  
Giovan N. Cholico ◽  
Daniel E. Perkins ◽  
Michael T. Fewkes ◽  
Julia Thom Oxford ◽  
...  
Keyword(s):  
Gene Expression ◽  
Extracellular Matrix ◽  
Liver Injury ◽  
Aryl Hydrocarbon Receptor ◽  
Receptor Activation ◽  
Matrix Remodeling ◽  
Mrna Levels ◽  
Gelatinase Activity ◽  
Ecm Remodeling ◽  
Aryl Hydrocarbon

The aryl hydrocarbon receptor (AhR) is a soluble, ligand-activated transcription factor that mediates the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Increasing evidence implicates the AhR in regulating extracellular matrix (ECM) homeostasis. We recently reported that TCDD increased necroinflammation and myofibroblast activation during liver injury elicited by carbon tetrachloride (CCl4). However, TCDD did not increase collagen deposition or exacerbate fibrosis in CCl4-treated mice, which raises the possibility that TCDD may enhance ECM turnover. The goal of this study was to determine how TCDD impacts ECM remodeling gene expression in the liver. Male C57BL/6 mice were treated for 8 weeks with 0.5 mL/kg CCl4, and TCDD (20 μg/kg) was administered during the last two weeks. Results indicate that TCDD increased mRNA levels of procollagen types I, III, IV, and VI and the collagen processing molecules HSP47 and lysyl oxidase. TCDD also increased gelatinase activity and mRNA levels of matrix metalloproteinase- (MMP-) 3, MMP-8, MMP-9, and MMP-13. Furthermore, TCDD modulated expression of genes in the plasminogen activator/plasmin system, which regulates MMP activation, and it also increased TIMP1 gene expression. These findings support the notion that AhR activation by TCDD dysregulates ECM remodeling gene expression and may facilitate ECM metabolism despite increased liver injury.

scholarly journals Myh10 deficiency leads to defective extracellular matrix remodeling and pulmonary disease

2018 ◽  
Author(s):  
Hyun-Taek Kim ◽  
Wenguang Yin ◽  
Young-June Jin ◽  
Paolo Panza ◽  
Felix Gunawan ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Alveolar Epithelium ◽  
Mouse Lung ◽  
Chain Gene ◽  
Matrix Remodeling ◽  
Ecm Remodeling ◽  
Muscle Myosin ◽  
Alveolar Formation ◽  
Deposition Defects

AbstractImpaired alveolar formation and maintenance are features of many pulmonary diseases that are associated with significant morbidity and mortality. In a forward genetic screen for modulators of mouse lung development, we identified the non-muscle myosin II heavy chain gene, Myh10. Myh10 mutant pups exhibit cyanosis and respiratory distress, and die shortly after birth from differentiation defects in alveolar epithelium and mesenchyme. From omics analyses and follow up studies, we find decreased Thrombospondin expression accompanied with increased matrix metalloproteinase activity in both mutant lungs and cultured mutant fibroblasts, as well as disrupted extracellular matrix (ECM) remodeling. Loss of Myh10 specifically in mesenchymal cells results in ECM deposition defects and alveolar simplification. Notably, MYH10 expression is down-regulated in the lung of emphysema patients. Altogether, our findings reveal critical roles for Myh10 in alveologenesis at least in part via the regulation of ECM remodeling, which may contribute to the pathogenesis of emphysema.

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