EM of human atherosclerosis: Aortic fatty streaks with transitional lesion features

1992 ◽  
Vol 50 (1) ◽  
pp. 622-623
Author(s):  
K. Florian Klemp ◽  
J.R. Guyton
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Processing Technique ◽  
Foam Cell Formation ◽  
Tissue Preparation ◽  
Electron Microscopic ◽  
Extracellular Lipid ◽  
Electron Microscopic Cytochemistry ◽  
Human Atherosclerosis ◽  
Clinically Significant

The earliest distinctive lesions in human atherosclerosis are fatty streaks (FS), characterized initially by lipid-laden foam cell formation. Fibrous plaques (FP), the clinically significant lesions, differ from FS in several respects. In addition to foam cells, the FP also exhibit fibromuscular proliferation and a necrotic core region rich in extracellular lipid. The possible transition of FS into mature FP has long been debated, however. A subset of FS described by Katz etal., was intermediate in lipid composition between ordinary FS and FP. We investigated this hypothesis by electron microscopic cytochemistry by employing a tissue processing technique previously described by our laboratory. Osmium-tannic acid-paraphenylenediamine (OTAP) tissue preparation enabled ultrastructural analysis of lipid deposits to discern features characteristic of mature fibrous plaques.

Abstract 43: Activation of the Nuclear Receptor Coactivator PGC-1α Mediates an Atheroprotective Effect

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Cathal McCarthy ◽  
Declan Mooney ◽  
Monica de Gaetano ◽  
William James ◽  
Desmond J Fitzgerald ◽  
...  
Keyword(s):  
Nuclear Receptor ◽  
Target Genes ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Nuclear Receptor Coactivator ◽  
Hub Gene ◽  
Cd36 Expression ◽  
Ppar Agonists ◽  
Human Atherosclerosis

Supplementing dietary chow with conjugated linoleic acid (CLA) induces marked regression of pre-established murine atherosclerosis, in contrast to other PPAR agonists. The finding suggests that there are unidentified endogenous pathways that suppress the progression or promote the regression of atherosclerosis. Identifying these pathways in the mouse and their homologues in humans may help elucidate the mechanisms of the disease and targets for future therapies. Here, we provide evidence that CLA inhibits foam cell formation via regulation of the nuclear receptor co-activator, PGC-1α in a manner that differs from PPAR activation. Gene expression analysis was performed in the aorta of ApoE -/- mice following induction of atherosclerosis and dietary supplementation with/without CLA. CLA induced dramatic regression of the cholesterol-induced atherosclerosis. PGC-1α was identified as a ‘hub’ gene within a cluster of genes induced by CLA in the aorta of the ApoE -/- during regression. PGC-1α protein was also found in murine and human atherosclerotic plaque, where it was localised to macrophage/foam cells. In a mouse macrophage cell line exposed to oxLDL, CLA induced PGC-1α and several genes in the network in an isomer specific fashion, including RORαand ABCA1. CLA also induced the PGC-1α target genes Cyp7b1 and UCP-1, and PPAR. CLA inhibited foam cell formation in the same cells exposed to oxLDL and suppressed the expression of the scavenger receptors, SRA-1 and CD36. Expression of the PGC-1α in macrophages had similar effects. Thus, over-expression of PGC-1α limited the accumulation of oxLDL and subsequent foam cell formation, while deletion of the gene promoted foam cell formation in bone marrow derived macrophages upon exposure to oxLDL. Moreover, deletion of PGC-1α prevented the inhibition of macrophages/foam cell formation by CLA. The nuclear receptor co-activator PGC-1α is a hub gene in a network of genes activated in the aorta during CLA-induced regression of atherosclerosis and mediates CLA’s inhibition of foam cell formation. PGC-1α is also is also expressed in human plaques where its expression is inversely associated with disease progression, raising the possibility that this pathway if activated could regulate human atherosclerosis.

Progression of foam-cell formation in vitro in elicited macrophages after incubation with ox-LDL

1994 ◽  
Vol 52 ◽  
pp. 210-211
Author(s):  
A.M. Klinkner ◽  
R. Waites ◽  
P. Bugelski ◽  
W. D. Kerns
Keyword(s):  
Electron Microscopy ◽  
Cultured Cells ◽  
Foam Cell ◽  
Neutral Lipids ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Nile Red ◽  
Ultrastructural Changes ◽  
Foam Cell Formation ◽  
Electron Microscopic

Thioglycollate elicited mouse peritoneal macrophages incubated with copper-oxidized LDL(ox-LDL) developed foam cell morphology as observed by Nile red fluorescent staining for neutral lipids and by electron microscopic observations. Total cellular cholesterol content rose steadily over 168 hrs and esterified vs free cholesterol ratios also increased.Cultured macrophages were incubated with ox-LDL, fixed, and stained with Nile red or processed for electron microscopy. Macrophages stained with Nile red exhibited progressive accumulation of lipid over 24, 72 and 168 hrs (Fig. 1-3). The percentage of cells with lipid inclusions and the size and number of inclusions per cell increased progressively over 168 hrs. Control cells incubated without ox-LDL did not have staining indicative of foam cell formation.Transmission electron microscopy of cultured cells at 24, 72, and 168 hrs showed distinct ultrastructural changes (Fig. 4-6). Macrophages at 24 hrs possessed non-membrane bound lipid droplets. Following 72 hrs, lysosomes containing multilamellar lipoid structures were also present. Cells at 168 hrs had characteristics similar to those at 24 and 72 hrs with the addition of cholesterol crystal profiles.

Early atherogenic events in the proximal aorta of the hyperlipidemic New Zealand white rabbit

1991 ◽  
Vol 49 ◽  
pp. 92-93
Author(s):  
K.F. Klemp ◽  
J.R. Guyton
Keyword(s):  
New Zealand ◽  
Neutral Lipid ◽  
Foam Cell ◽  
Cell Formation ◽  
Zealand White Rabbit ◽  
Foam Cell Formation ◽  
New Zealand White Rabbit ◽  
Subendothelial Space ◽  
Extracellular Lipid ◽  
Cytochemical Technique

The earliest recognized atherogenic event in the cholesterol-fed New Zealand White Rabbit is the accumulation of extracellular lipid in the subendothelial space. This event, which was reported to precede foam cell formation, is probably the result of transcytosis by the endothelium of β-VLDL particles which circulate in excess in the blood due to hyperlipidemia. The extracellular lipid was described as being uni or multilamellar vesicles consisting of phospholipid and unesterified cholesterol, β-VLDL particles, however, contain cholesteryl ester as their major lipid constituent and the presence of this neutral lipid was not demonstrated due to its extraction by dehydrating solvents. A lipid cytochemical technique that allows visualization of both vesicular and neutral lipid was developed in our laboratory and was employed to study this early lipid deposition.

Aged Garlic Extract Inhibits CD36 Expression and Foam Cell Formation in Human Macrophages

Planta Medica ◽  
2007 ◽  
Vol 73 (09) ◽  
Author(s):  
N Ide ◽  
N Morihara ◽  
L Paptheodorou ◽  
R Stirner ◽  
N Weiss
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Garlic Extract ◽  
Foam Cell Formation ◽  
Aged Garlic Extract ◽  
Human Macrophages ◽  
Cd36 Expression ◽  
Aged Garlic

Dynamic Role of Macrophage Sub Types for Development of Atherosclerosis and Potential Use of Herbal Immunomodulators as Imminent Therapeutic Strategy

2020 ◽  
Vol 18 ◽  
Author(s):  
Parimalanandhini Duraisamy ◽  
Sangeetha Ravi ◽  
Mahalakshmi Krishnan ◽  
Catherene M. Livya ◽  
Beulaja Manikandan ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Foam Cell Formation ◽  
Atherosclerosis Progression ◽  
Proinflammatory Mediators ◽  
M1 Macrophage ◽  
Tnf Α ◽  
Inflammatory Site

: Atherosclerosis, a major contributor to cardiovascular disease is a global alarm causing mortality worldwide. Being a progressive disease in the arteries, it mainly causes recruitment of monocytes to the inflammatory sites and subside pathological conditions. Monocyte-derived macrophage mainly acts in foam cell formation by engorging the LDL molecules, oxidizes it into Ox-LDL and leads to plaque deposit development. Macrophages in general differentiate, proliferate and undergo apoptosis at the inflammatory site. Frequently two subtypes of macrophages M1 and M2 has to act crucially in balancing the micro-environmental conditions of endothelial cells in arteries. The productions of proinflammatory mediators like IL-1, IL-6, TNF-α by M1 macrophage has atherogenic properties majorly produced during the early progression of atherosclerotic plaques. To counteract cytokine productions and M1-M2 balance, secondary metabolites (phytochemicals) from plants act as a therapeutic agent in alleviating atherosclerosis progression. This review summarizes the fundamental role of the macrophage in atherosclerotic lesion formation along with its plasticity characteristic as well as recent therapeutic strategies using herbal components and anti-inflammatory cytokines as potential immunomodulators.

ClC-3: A Novel Promising Therapeutic Target for Atherosclerosis

2021 ◽  
pp. 107424842110236
Author(s):  
Dun Niu ◽  
Lanfang Li ◽  
Zhizhong Xie
Keyword(s):  
Therapeutic Target ◽  
Chloride Channels ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Molecular Structures ◽  
Foam Cell Formation ◽  
Endothelium Dysfunction ◽  
Atherosclerotic Process

Chloride channel 3 (ClC-3), a Cl−/H+ antiporter, has been well established as a member of volume-regulated chloride channels (VRCCs). ClC-3 may be a crucial mediator for activating inflammation-associated signaling pathways by regulating protein phosphorylation. A growing number of studies have indicated that ClC-3 overexpression plays a crucial role in mediating increased plasma low-density lipoprotein levels, vascular endothelium dysfunction, pro-inflammatory activation of macrophages, hyper-proliferation and hyper-migration of vascular smooth muscle cells (VSMCs), as well as oxidative stress and foam cell formation, which are the main factors responsible for atherosclerotic plaque formation in the arterial wall. In the present review, we summarize the molecular structures and classical functions of ClC-3. We further discuss its emerging role in the atherosclerotic process. In conclusion, we explore the potential role of ClC-3 as a therapeutic target for atherosclerosis.

scholarly journals Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation

2021 ◽  
Vol 14 (6) ◽  
pp. 567
Author(s):  
Su Wutyi Thant ◽  
Noppawan Phumala Morales ◽  
Visarut Buranasudja ◽  
Boonchoo Sritularak ◽  
Rataya Luechapudiporn
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Raw 264.7 ◽  
Low Density ◽  
Lipoprotein Oxidation ◽  
Raw 264.7 Macrophage Cells ◽  
Low Density Lipoprotein Oxidation

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

L-theanine inhibits foam cell formation via promoting the scavenger receptor A degradation

2021 ◽  
pp. 174181
Author(s):  
Jianzhen Lei ◽  
Jingheng Ye ◽  
Rong She ◽  
Ruyi Zhang ◽  
Yanan Wang ◽  
...  
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Scavenger Receptor A

scholarly journals Glucose-Dependent Insulinotropic Polypeptide Suppresses Foam Cell Formation of Macrophages through Inhibition of the Cyclin-Dependent Kinase 5-CD36 Pathway

Biomedicines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 832
Author(s):  
Michishige Terasaki ◽  
Hironori Yashima ◽  
Yusaku Mori ◽  
Tomomi Saito ◽  
Yoshie Shiraga ◽  
...  
Keyword(s):  
Gene Expression ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
U937 Cells ◽  
Cyclin Dependent Kinase ◽  
Macrophage Foam Cell ◽  
Cyclin Dependent Kinase 5 ◽  
Gip Receptor ◽  
Cd36 Gene

Glucose-dependent insulinotropic polypeptide (GIP) has been reported to have an atheroprotective property in animal models. However, the effect of GIP on macrophage foam cell formation, a crucial step of atherosclerosis, remains largely unknown. We investigated the effects of GIP on foam cell formation of, and CD36 expression in, macrophages extracted from GIP receptor-deficient (Gipr−/−) and Gipr+/+ mice and cultured human U937 macrophages by using an agonist for GIP receptor, [D-Ala2]GIP(1–42). Foam cell formation evaluated by esterification of free cholesterol to cholesteryl ester and CD36 gene expression in macrophages isolated from Gipr+/+ mice infused subcutaneously with [D-Ala2]GIP(1–42) were significantly suppressed compared with vehicle-treated mice, while these beneficial effects were not observed in macrophages isolated from Gipr−/− mice infused with [D-Ala2]GIP(1–42). When macrophages were isolated from Gipr+/+ and Gipr−/− mice, and then exposed to [D-Ala2]GIP(1–42), similar results were obtained. [D-Ala2]GIP(1–42) attenuated ox-LDL uptake of, and CD36 gene expression in, human U937 macrophages as well. Gene expression level of cyclin-dependent kinase 5 (Cdk5) was also suppressed by [D-Ala2]GIP(1–42) in U937 cells, which was corelated with that of CD36. A selective inhibitor of Cdk5, (R)-DRF053 mimicked the effects of [D-Ala2]GIP(1–42) in U937 cells. The present study suggests that GIP could inhibit foam cell formation of macrophages by suppressing the Cdk5-CD36 pathway via GIP receptor.

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