scholarly journals Comparative immunohistochemical and morphometric research of interleukin-17 in various atherosclerotic lesions in human

2020 ◽  
Author(s):  
Petr V. Pigarevsky ◽  
Vlada A Snegova ◽  
Svetlana V. Maltseva ◽  
Natalia G. Davydova
Keyword(s):  
Atherosclerotic Plaque ◽  
Mononuclear Cells ◽  
Atherosclerotic Plaques ◽  
Interleukin 17 ◽  
Atherosclerotic Lesions ◽  
Th 17 ◽  
Unstable Atherosclerotic Plaque ◽  
First Time ◽  
Inflammatory Action

The aim of the artical to investigate cellular and tissue localization of IL-17 in various atherosclerotic lesions of arteries of human and on the basis of the obtained data to make a hypothesis of a possible role of Th-17 of cells in destabilization of an atherosclerotic plaque. Material and methods. On autopsy material by means of histologic, immunohistochemical and morphometric research techniques aorta segments, the coronary arteries and a.basilaris with various types of atherosclerotic lesions (43 samples of tissue) were studied. In samples of tissue studied the endothelial and mononuclear cells expressing interleukin-17. Results. It is shown that endothelial cells of an intima are capable to produce IL-17 in all types of atherosclerotic plaques. Increase in number of the mononuclear cells expressing IL-17 in an intima of arteries was at the same time revealed. It is shown that the maximum number of the cells expressing IL-17 was found in an intima of an unstable atherosclerotic plaque, it is especially frequent around a rupture of its cap. What can demonstrate pro-inflammatory action of Th - 17 - cells and IL-17 expressed by them and significant effect them on formation of unstable atherosclerotic lesions. Conclusion. On the basis of the obtained data for the first time it was succeeded to make a hypothesis of a possible role of Th-17 of cells in destabilization of an atherosclerotic plaque.

Abstract 511: Mrp8 And Mrp14,Endogenous Activators of Toll-lLke Receptor4, are Associated with Rupture-Prone Human Atherosclerotic Plaques

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Mihaela G Ionita ◽  
Gerard Pasterkamp ◽  
Dominique deKleijn
Keyword(s):  
Atherosclerotic Plaque ◽  
Atherosclerotic Plaques ◽  
Atherosclerotic Lesions ◽  
Inflammatory Status ◽  
Potential Marker ◽  
Plaque Phenotype ◽  
Histological Characteristics ◽  
Unstable Plaques ◽  
Human Carotid

Objectives : Atherosclerosis is a chronic, complex inflammatory process and is the underlying cause of stroke and myocardial infarction due to rupture of the atherosclerotic plaque leading to acute occlusion of the artery in the brain or heart. Macrophages, infiltrating atherosclerotic lesions, abundantly express Mrp8 and Mrp14. Recently Mrp8, Mrp14 and the complex Mrp8/14 have been identified as endogenous ligands of Tlr-4.The role of Tlr-4 in the development and progression of the atherosclerotic plaque is well recognized and it is associated with a rupture-prone plaque phenotype. Expression of Mrps in human plaques and its relation to plaque phenotype is unknown. For this, we investigated the levels of Mrp8, Mrp14 and Mrp8/14 complex in a large number of human atherosclerotic plaques. Methods and results : Mrp8, Mrp14 and Mrp8/14 were quantified by ELISAs in human carotid endarterectomy specimens (186 patients) and plaque phenotype was determined by immunohistochemistry. Mrp levels were higher in the unstable (58 fibro-atheromatous, 64 atheromatous) compared to the stable (64 fibrous) plaques: Mrp8 p = 0.001 ; Mrp14 p = 0.001 ; Mrp8/14 p = 0.01 . Concomitantly, Mrp8, Mrp14 and Mrp8/14 were associated with characteristics of unstable plaques: more macrophages ( p = 0.024; p = 0.002; p = 0.076 ), less smooth muscle cells ( p = 0.041; p = 0.001; p = 0.074 ), larger lipid core ( p = 0.001; p = 0.001; p=0.004 ), less collagen ( p = 0.440; p = 0.011; p = 0.372 ). Furthermore, Mrp plaque levels were positively correlated with the pro-inflammatory cytokines (IL-6 and IL-8) and matrix metalloproteinsases (MMP2, MMP8 and MMP9) plaque levels. EDA, marker of stable plaques, was negatively associated with Mrps plaque levels. Histological analysis revealed that Mrps are expressed by a subgroup of plaque macrophages localized in the plaque cap and shoulder, the most rupture-prone sites of an atherosclerotic plaque. Conclusions: We show that Mrp8, Mrp14 and Mrp8/14 are strongly associated with the histological characteristics and inflammatory status of human rupture-prone plaques and identify Mrps as a potential marker for rupture-prone plaques.

Abstract 340: The Expression and Function of Apol6 in Atherosclerotic Plaques of Apoe -/- Mouse Aorta Tissue

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Siqin Zhaorigetu ◽  
Chien-An A Hu ◽  
Warren Laskey ◽  
Brian Walton
Keyword(s):  
Atherosclerotic Plaque ◽  
Sirna Delivery ◽  
Aortic Tissue ◽  
Atherosclerotic Plaques ◽  
Plaque Instability ◽  
Atherosclerotic Lesions ◽  
And Function ◽  
Mouse Aorta

Background: We recently demonstrated that apolipoprotein L6 (ApoL6) regulates apoptosis and autophagy in atherosclerotic lesions, implying that ApoL6 is an important factor that causes plaque instability and a potential therapeutic target for treating atherosclerosis. To further investigate the role of ApoL6 in atherogenesis in vivo , the expression of ApoL6 was knocked down by the liposome-siRNA strategy in the aorta tissue of ApoE -/- mouse. Methods: Liposomal siRNAs were prepared by using the thin-film hydration method and were labeled with quantum dots (QD). ApoE -/- mice were intravenously injected twice in 1 week with either liposomal control siRNA-QD or liposomal ApoL6 siRNA-QD. We harvested aortic tissue from mice and used immunofluorescence staining to analyze the expression of ApoL6 in atherosclerotic plaque. Results: Immunofluorescence analysis showed that expression of ApoL6 was elevated in the atherosclerotic plaque and partially co-localized with a macrophage marker CD68 in ApoE -/- mouse. The results suggest a link between ApoL6 and macrophages in the pathobiology of atherosclerotic lesions ( Fig. A and B ). Confocal microscopy images showed that liposomal ApoL6 siRNA significantly reduced ApoL6 expression (green punctures) in atherosclerotic plaques as compared with liposomal control siRNA (Fig. C) . Conclusion: We established a silencing model of ApoL6 in cardiovascular system of ApoE -/- mouse using liposome-mediated siRNA delivery system. The intravenous injection of liposomal ApoL6 siRNA silences ApoL6 expression in the aortas of ApoE -/- mice and may protect against the development of atherosclerosis.

scholarly journals The role of cell proliferation in atherogenesis and in the destabilization of atherosclerotic plaque in human

2019 ◽  
Vol 19 (2) ◽  
pp. 7-12
Author(s):  
Peter V. Pigarevsky ◽  
Olga G. Yakovleva ◽  
Svetlana V. Maltseva ◽  
Veronica A. Guseva
Keyword(s):  
Cell Proliferation ◽  
Atherosclerotic Plaque ◽  
Vascular Wall ◽  
Original Data ◽  
Atherosclerotic Plaques ◽  
Proliferating Cells ◽  
Experimental Animals ◽  
Atherosclerotic Lesions

The review examined of the processes of cell proliferation in human vascular wall and experimental animals during the formation of atherosclerotic plaques. Shows the types of actively proliferating cells: lymphocytes, macrophages, endotheliocytes and zones identified in the vascular wall, where this proliferation occurs. The factors that promote and hinder cell proliferation during the growth of atherosclerotic plaque are identified. The survey shows all the stages of the formation of atherosclerotic lesions, ranging from normal plots and lipid stains to pronounced fibrous plaques. Establishes a link between the cell proliferation and inflammation in the vascular wall man. Separately considered the role of cell proliferation in the destabilization of atherosclerotic plaque. If atherosclerosis this process still poorly studied, in the formation of unstable atherosclerotic plaques in humans it is completely unknown. Based on your own original data was finally on the important role of the processes of cell proliferation in the formation of unstable atherosclerotic plaques in humans.

Comparison of two murine models of thrombosis induced by atherosclerotic plaque injury

2011 ◽  
Vol 105 (S 06) ◽  
pp. S3-S12 ◽  
Author(s):  
Béatrice Hechler ◽  
Christian Gachet
Keyword(s):  
Atherosclerotic Plaque ◽  
Plaque Rupture ◽  
Vascular Lesions ◽  
Murine Models ◽  
Atherosclerotic Lesions ◽  
Human Pathology ◽  
Rupture Model ◽  
Atherosclerotic Plaque Rupture ◽  
Collagen Receptor

SummaryArterial thrombosis occurs at sites of erosion or rupture of atherosclerotic vascular lesions. To better study the pathophysiology of this complex phenomenon, there is a need for animal models of localised thrombosis at sites of atherosclerotic lesions with closer resemblance to the human pathology as compared to commonly used thrombosis models in healthy vessels. In the present study, we describe and compare a new model of thrombosis induced by atherosclerotic plaque rupture in the carotid artery from ApoE-/- mice using a suture needle to a milder model of ultrasound-induced plaque injury. Needle injury induces atherosclerotic plaque rupture with exposure of plaque material and formation of a thrombus that is larger, nearly occlusive and more stable as compared to that formed by application of ultrasounds. These two models have common features such as the concomitant involvement of platelet activation, thrombin generation and fibrin formation, which translates into sensitivity toward both antiplatelet drugs and anticoagulants. On the other hand, they display differences with respect to the role of the platelet collagen receptor GPVI, the plaque rupture model being less sensitive to its inhibition as compared to the ultrasound-induced injury, which may be related to the amount of thrombin generated. These models represent an improvement as compared to models in healthy vessels and may help identify specific plaque triggers of thrombosis. They should therefore be useful to evaluate new antithrombotic targets.

scholarly journals The Role of Smooth Myocytes and Macrophages in Development of Complicated Forms of Arterial Atherosclerosis

Kardiologiia ◽  
2019 ◽  
Vol 59 (1) ◽  
pp. 57-61
Author(s):  
S. S. Todorov
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Immunohistochemical Study ◽  
Muscle Cells ◽  
External Carotid ◽  
Atherosclerotic Plaques ◽  
Unstable Atherosclerotic Plaque ◽  
Immunohistochemical Studies ◽  
Smooth Myocytes

Purpose:to conduct morphohistochemical and immunohistochemical study of arterial unstable atherosclerotic plaques for assessment of the state of smooth muscle cells (SMC) and macrophages.Materials and methods.The surgical material of the peripheral arteries (femoral, popliteal, external carotid) was obtained from 50 patients aged over 60 years, followed by morphohistochemical, immunohistochemical studies.Results.Hyperplasia of secretory smooth muscle cells (SMC), and new formation of thin-walled capillary vessels was noted in unstable atherosclerotic plaques. Macrophagic infiltration was detected in the intima of arteries, in places of accumulation of foam cells.Conclusion.Unstable atherosclerotic plaque is a cellular-intercellular process with the participation of lipids, macrophages, and with predominance of SMC and newly formed vessels.

scholarly journals Gene Expression Profiling in Fibromyalgia Indicates an Autoimmune Origin of the Disease and Opens New Avenues for Targeted Therapy

2020 ◽  
Vol 9 (6) ◽  
pp. 1814 ◽  
Author(s):  
Marzia Dolcino ◽  
Elisa Tinazzi ◽  
Antonio Puccetti ◽  
Claudio Lunardi
Keyword(s):  
Gene Expression ◽  
Mononuclear Cells ◽  
Clinical Manifestations ◽  
Interleukin 17 ◽  
Type I ◽  
Peripheral Blood Mononuclear ◽  
Th 17 ◽  
Chronic Disorder ◽  
Non Coding Rnas ◽  
Pain Symptoms

Fibromyalgia is a chronic disorder characterized by widespread pain and by several non-pain symptoms. Autoimmunity, small fiber neuropathy and neuroinflammation have been suggested to be involved in the pathogenesis of the disease. We have investigated the gene expression profile in peripheral blood mononuclear cells obtained from ten patients and ten healthy subjects. Of the 545,500 transcripts analyzed, 1673 resulted modulated in fibromyalgic patients. The majority of these genes are involved in biological processes and pathways linked to the clinical manifestations of the disease. Moreover, genes involved in immunological pathways connected to interleukin-17 and to Type I interferon signatures were also modulated, suggesting that autoimmunity plays a role in the disease. We then aimed at identifying differentially expressed Long non-coding RNAs (LncRNAs) functionally connected to modulated genes both directly and via microRNA targeting. Only two LncRNAs of the 298 found modulated in patients, were able to target the most highly connected genes in the fibromyalgia interactome, suggesting their involvement in crucial gene regulation. Our gene expression data were confirmed by real time PCR, by autoantibody testing, detection of soluble mediators and Th-17 polarization in a validation cohort of 50 patients. Our results indicate that genetic and epigenetic mechanisms as well as autoimmunity play a pivotal role in the pathogenesis of fibromyalgia.

Unexpected Evidence That Dimethylsulphoxide (DMSO) Upregulates Expression of CXCR4 on Hematopoietic Stem/Progenitor Cells (HSPC), Increases Their Responsiveness to an SDF-1 Gradient and Enhances Homing to Bone Marrow.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1973-1973
Author(s):  
Marcin Majka ◽  
Danuta Jarocha ◽  
Marcin Wysoczynski ◽  
Duygu Sag ◽  
Ewa Zuba-Surma ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Short Exposure ◽  
Hematopoietic Stem ◽  
Akt Phosphorylation ◽  
Human Cd34 ◽  
New Strategy ◽  
First Time

Abstract Cryopreservation of bone marrow (BM), mobilized peripheral blood (mPB) and cord blood (CB) cells is a routine procedure to store hematopoietic stem/progenitor cells (HSPC) for transplantation. Dimethylsulphoxide (DMSO), the most commonly used cryoprotectant, is toxic to cells at higher concentrations (>10%); moreover, the freezing-thawing procedure itself is inevitably connected with the loss of HSPC. However, by chance we observed that short exposure of HSPC to DMSO enhances the responsiveness of these cells to an SDF-1 gradient and since SDF-1 is a major chemoattractant that navigates homing of HSPC to BM we became interested in elucidating this phenomenon. We found that short incubation (5–10 min) of human CB mononuclear cells (MNC) with DMSO at concentrations employed for cryopreservation (5–10%) significantly upregulates the expression of both CXCR4 (x 2–3) and CD34 (x 1.5) on CB MNC (as measured by FACS). Furthermore, DMSO significantly increased the chemotactic responsiveness (x 2–4) of CB MNC, BM MNC and selected CXCR4+ human hematopoietic cell lines (Jurkat, THP-1 cells) when the cells were exposed to 5–10% DMSO before chemotaxis assay. These responses to an SDF-1 gradient correlated with enhanced chemotaxis also of human CD34+, CD34+ CD38+, CD34+ CD38−, and CD34+ CXCR4+ clonogeneic progenitor cells, suggesting that DMSO directly enhances the responsiveness of human early progenitors (p<0.0001). At the molecular level, 5–10% DMSO strongly stimulated and prolonged SDF-1-dependent AKT phosphorylation. However, at the same time DMSO inhibited phosphorylation of MAPKp42/44. Similar observations were made for Sca-1+ BM-derived murine cells. In parallel experiments we found that murine Sca-1+ cells when preincubated with DMSO formed more 12 day-CFU-S colonies in spleens after transplantation into irradiated syngeneic recipients. Accordingly, x 2 more CFU-S were formed when Sca-1+ cells were exposed before transplantation to 5% DMSO and about x 4 more after exposure to 10% DMSO. Finally we employed a Ly5.1/Ly5.2 congeneic transplant model and showed that transplantation of Ly5.1 Sca-1+ cells exposed to 10% DMSO before transplantation resulted in higher chimerism in transplanted Ly5.2 mice as compared to untreated cells (control) (p<0.0001). In conclusion, we show for the first time an unexpected beneficial role of DMSO (5–10%) in regulation of homing of HSPC after transplantation and suggest that a short priming of HSPC with DMSO, even of non-cryopreserved cells, before transplantation may become a new strategy to enhance engraftment

Dopamine signaling attenuated myocardial injury during endotoxemia

2018 ◽  
Vol 6 (1) ◽  
pp. 33-43
Author(s):  
Mark Turler ◽  
Shel Thoma
Keyword(s):  
Mononuclear Cells ◽  
Intraperitoneal Administration ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tunel Staining ◽  
Lv Function ◽  
Myocardial Apoptosis ◽  
D2 Antagonist ◽  
Dopamine Signaling ◽  
First Time

Myocardial depression is a well-recognized manifestation of organ dysfunction in sepsis, the direct protective effect of Dopamine on myocardial is still not clear. Here, we aimed to study whether Dopamine can directly protect myocardial from endotoxemia. To test that, we used adult C57/BL6 mice were treated with endotoxin (0.5 mg/kg, iv). Clozapine was administered as D2 antagonist, (intraperitoneal administration shortly before the model of sepsis). Electron microscopy, TUNEL staining, caspase-3 expression, and the Bcl-2/Bax ratio were used to measure myocardial apoptosis. Left ventricle (LV) function was assessed using a microcatheter system. Chemokines and cytokines in plasma and myocardium were analyzed by enzyme-linked immunosorbent assay (ELISA). Mononuclear cells in the myocardium were examined using immunofluorescence staining. In conclusion, our results for the first time showed the role of Dopamine to directly protect myocardial from endotoxemia through attenuated proinflammatory cytokines and partly through inhibiting apoptosis.

scholarly journals Ferryl Hemoglobin and Heme Induce Α1-Microglobulin in Hemorrhaged Atherosclerotic Lesions with Inhibitory Function against Hemoglobin and Lipid Oxidation

2021 ◽  
Vol 22 (13) ◽  
pp. 6668
Author(s):  
Dávid Pethő ◽  
Tamás Gáll ◽  
Zoltán Hendrik ◽  
Annamária Nagy ◽  
Lívia Beke ◽  
...  
Keyword(s):  
Radical Scavenging ◽  
Cell Types ◽  
Oxidative Modification ◽  
Atherosclerotic Plaques ◽  
Aortic Endothelial Cells ◽  
Inhibitory Function ◽  
Atherosclerotic Lesions ◽  
Atheromatous Plaques ◽  
Heme Binding Protein

Infiltration of red blood cells into atheromatous plaques and oxidation of hemoglobin (Hb) and lipoproteins are implicated in the pathogenesis of atherosclerosis. α1-microglobulin (A1M) is a radical-scavenging and heme-binding protein. In this work, we examined the origin and role of A1M in human atherosclerotic lesions. Using immunohistochemistry, we observed a significant A1M immunoreactivity in atheromas and hemorrhaged plaques of carotid arteries in smooth muscle cells (SMCs) and macrophages. The most prominent expression was detected in macrophages of organized hemorrhage. To reveal a possible inducer of A1M expression in ruptured lesions, we exposed aortic endothelial cells (ECs), SMCs and macrophages to heme, Oxy- and FerrylHb. Both heme and FerrylHb, but not OxyHb, upregulated A1M mRNA expression in all cell types. Importantly, only FerrylHb induced A1M protein secretion in aortic ECs, SMCs and macrophages. To assess the possible function of A1M in ruptured lesions, we analyzed Hb oxidation and heme-catalyzed lipid peroxidation in the presence of A1M. We showed that recombinant A1M markedly inhibited Hb oxidation and heme-driven oxidative modification of low-density lipoproteins as well plaque lipids derived from atheromas. These results demonstrate the presence of A1M in atherosclerotic plaques and suggest its induction by heme and FerrylHb in the resident cells.

Sign in / Sign up

Export Citation Format

Share Document