SEARCH · Search PubMed

Results for “Foam Cells”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 73 records · Page 4Linked to original sources

PubMed1992

Lipoprotein lipase is synthesized by macrophage-derived foam cells in human coronary atherosclerotic plaques.

Lipoprotein lipase (LPL), hydrolyzes the core triglycerides of lipoproteins, thereby playing a role in their maturation. LPL may be important in the metabolic pathways that lead to atherosclerosis, since it is secreted in vitro by both of the predominant cell types of the atherosclerotic plaque, i.e., macrophages and smooth muscle cells. Because of uncertainty concerning the primary cellular source of LPL in atherosclerotic lesions, in situ hybridization assays for LPL mRNA were performed on 12 coronary arteries obtained from six cardiac allograft recipients. Macrophages and smooth muscle cells were identified on adjacent sections with cell-specific antibodies and foam cells were identified morphologically. LPL protein was localized using a polyclonal antibody. LPL mRNA was produced by a proportion of plaque macrophages, particularly macrophage-derived foam cells, but was not detected in association with any intimal or medial smooth muscle cells. These findings were confirmed by combined immunocytochemistry and in situ hybridization on the same tissue sections. LPL protein was detected in association with macrophage-derived foam cells, endothelial cells, adventitial adipocytes, and medial smooth muscle cells, and, to a lesser extent, in intimal smooth muscle cells and media underlying well-developed plaque. These results indicate that macrophage-derived foam cells are the primary source of LPL in atherosclerotic plaques and are consistent with a role for LPL in the pathogenesis of atherosclerosis.

Arteriosclerosis↗

PubMed1997

Human beta-migrating very low density lipoprotein induces foam cell formation in human mesangial cells.

To elucidate the mechanism of foam cell formation in the mesangial region of a kidney observed in a familial type III hyperlipoproteinemic patient presenting with diabetes mellitus and nephrotic syndrome, we have examined, in the present study, the effect of human beta-VLDL (apo E2/E2) on foam cell formation in human mesangial cells, since an increase in beta-VLDL is a characteristic feature of this patient. Human beta-VLDL (apo E2/E2) induced foam cell formation in human mesangial cells. The binding of [125I]LDL to human mesangial cells was inhibited completely by both LDL and beta-VLDL. On the other hand, the binding of [125I]beta-VLDL was completely inhibited by beta-VLDL, but partially by LDL. The LDL receptor, but not the VLDL receptor was down-regulated by accumulation of cholesteryl esters. These results suggest that human beta-VLDL (apo E2/E2)-induced foam cell formation in mesangial cells is mediated through both the LDL receptor pathway and the beta-VLDL specific pathway, in which the VLDL receptor is one of the candidates.

Blotting, Northern↗

PubMed1990

[DNA synthesis in the foam cells of the vascular wall in experimental atherosclerosis in rabbits].

Proliferative activity of the aortic intima cells in the course of experimental rabbit hypercholesterolemia is studied. The most intensive DNA synthesis was found in macrophages and smooth cells transforming into the foam cells as shown by electron-microscopic radioautographic analysis. DNA synthesis by damaged and dying foam cells is shown. Cytophotometric analysis showed the small proportion of foam cells in the atherosclerotic lesions to be polyploid.

Animals↗

PubMed1994

Enhanced LDL oxidation by murine macrophage foam cells and their failure to secrete nitric oxide.

Foam cells were produced in vitro by incubation of mouse peritoneal macrophages with acetylated or copper-oxidized LDL. Nitric oxide synthesis was stimulated by exposure of the cells to IFN gamma and LPS. Nitric oxide production, detected by measurement of nitrite in the culture medium, was unchanged in Ac-LDL loaded cells as compared with non-loaded cells. However, Ox-LDL foam cells produced 68-99% less nitrite than non-loaded cells. Failure to detect nitric oxide synthase (NOS) products from macrophages previously loaded with Ox-LDL appeared to result from lack of NOS activity, as little active enzyme could be recovered from Ox-LDL loaded cells. However, addition of Ox-LDL to an active cell-free NOS preparation had no direct effect on enzymic activity. When native LDL was subsequently incubated with these various IFN gamma/LPS stimulated cells, cells pre-loaded with Ox-LDL promoted, on average, a 2-fold greater increase in oxidative modification of the LDL added than either non-loaded or Ac-LDL loaded cells. That is, there was an inverse correlation between NOS activity and the ability of the cells to promote LDL oxidation. Unstimulated Ox-LDL loaded foam cells also oxidized LDL better than unstimulated non-loaded or Ac-LDL loaded foam cells, and the extent of oxidative modification was generally greater than seen with the equivalent IFN gamma/LPS stimulated cells. This suggests that Ox-LDL loading also affects some additional factor(s) responsible for cell-mediated LDL oxidation.

Acetylation↗

PubMed2002

Expression of the myeloid-specific leukocyte integrin gene CD11d during macrophage foam cell differentiation and exposure to lipoproteins.

The leukocyte integrin gene CD11d is expressed predominantely on subsets of the myelomonocytic lineage (myeloid cells), particularly on macrophage foam cells and splenic red pulp macrophages. Its expression pattern clearly differs from myeloid-specific leukocyte integrins CD11b and CD11c and the leukocyte-specific integrin CD11a. Although the functions of CD11d have not been determined in any detail, its expression in these cell types suggests that it may play a role in the atherosclerotic process. To better understand how this gene is regulated, the steady-state level of CD11d mRNA in differentiating bone marrow CD34+CD38- cells, peripheral blood monocytes, and monocytic cell lines was assessed by Northern blot analysis and RT-PCR and compared with those of CD11a, CD11b, and CD11c. Expression of CD11d occurs early in CD34+CD38- cells, rises, and then decreases, in contrast to the expression of the other leukocyte integrins. Expression of CD11d reappears in peripheral blood monocytes differentiating to macrophage foam cells. Oxidized lipoproteins (OxLDL) and acetylated lipoproteins (AcLDL) failed to upregulate CD11d following differentiation of peripheral blood monocytes or the monocytic cell line HL60. However, when both OxLDL and AcLDL were present during differentiation, CD11d was further upregulated. This suggests that expression of CD11d is coordinately regulated with expression of LDL receptors and the development of the foam cell. Site-directed mutagenesis of the -100 to -20 region of the CD11d promoter revealed transcription factor binding sites essential for expression of this gene. Decoy oligonucleotides to the -100 to -20 region taken up by CD34+CD38- cells block their differentiation into myeloid colonies. This suggests that one or more transcription factors that regulate CD11d also are essential for myeloid differentiation, and that the CD11d promoter may be used as a model gene to identify transcription factors essential for myeloid cell differentiation.

CD11 Antigens↗

PubMed1994

[A case of IgA nephropathy with numerous interstitial foam cells--analysis of infiltrating mononuclear leucocytes in renal tissue].

A 27-year-old female was admitted to our hospital in order to examine proteinuria and microscopic hematuria. Light microscopic findings of her kidney showed proliferation of mesangial cells and numerous interstitial foam cells. Immunofluorescent and electron microscopic findings revealed IgA nephropathy. Immunoperoxidase studies using monoclonal antibodies disclosed that interstitial foam cells were positive for antibodies of the monocyte/macrophage lineage and also expressed adhesion molecules (CD11a, b, c, LFA-1) and MHC-class II antigens. Hereditary nephritis as Alport syndrome was negated by her familial history and electron microscopic study. We considered that it was a rare and interesting case with numerous interstitial foam cells, because the patient did not have hyperlipidemia as in nephrotic syndrome.

Adult↗

PubMed1993

Gap junctional communication between vascular cells. Induction of connexin43 messenger RNA in macrophage foam cells of atherosclerotic lesions.

The structure and function of blood vessels depend on the ability of vascular cells to receive and transduce signals and to communicate with each other. One means by which vascular cells have been shown to communicate is via gap junctions, specifically connexin43. In atherosclerosis, the normal physical patterns of communication are disrupted by the subendothelial infiltration and accumulation of blood monocytes, which in turn can differentiate into resident foam cells. In this paper we report that neither freshly isolated human peripheral blood monocytes nor differentiated monocytes/macrophages exhibit functional gap junctional dye transfer in homo-cellular culture or in co-culture with endothelial cells or smooth muscle cells. By Northern analysis, neither freshly isolated blood monocytes nor pure cultures of differentiated monocyte/macrophages expressed gap junction messenger RNA. However, immunohistochemical staining followed by in situ hybridization on sections of human atherosclerotic carotid arteries revealed strong expression of gap junction connexin43 messenger RNA by macrophage foam cells. These results suggest that tissue-specific conditions present in atherosclerotic arteries induce expression of connexin43 messenger RNA in monocyte/macrophages.

Arteriosclerosis↗

PubMed1976

[Role of foam cells in lipoprotein transformation within the vascular wall].

Foam cells were isolated from atherosclerotic aortas of rabbits following their intima incubation with collagenase and elastase. The viability of the cells, their incidence and nativity were supported histochemically and electron-microscopically. The interaction of the foam cells with lipoproteins was studied in vitro with perfusions of isolated atherosclerotic aortas of rabbits during 6 hours with a medium containing beta- and pre-beta-lipoproteins labelled with I125 or simultaneously with I125 and C14-cholesterol. It was found that after the perfusion the foam cells contain a much higher proportion of radioactivity of the total lipids, cholesterol and cholesterol esters, to that of the proteins, than the perfusate. The foam cells must selectively "capture" the lipids from the lipoprotein particles. The proportion "free cholesterol/cholesterol esters" (according to the radioactivity) proved to be much higher in the foam cells than in the perfusate. The possible mechanisms of the participation of the foam cells in the metabolism of lipoproteins and in the pathogenesis of atherosclerosis are discussed.

Animals↗

PubMed2003

Proteomic studies of macrophage-derived foam cell from human U937 cell line using two-dimensional gel electrophoresis and tandem mass spectrometry.

SUMMARY: The authors have identified 37 proteins in the whole-cell extracts from human monoblastic leukemia (U937) cell and macrophage-derived foam cell. The in vitro foam cell model was established by incubating the human U937 cells with oxidized low-density lipoprotein. The global changes in protein expressions between U937 foam cell and normal U937 cells were measured with two-dimensional polyacrylamide gel electrophoresis, and some proteins were trypsin-digested and then identified through tandem mass spectrometry after capillary liquid chromatography separation. Some of the identified proteins were validated via Internet links to the U937 proteomic map provided on the Expasy proteomics server. The experimental data can provide potential markers for atherosclerotic studies.

Electrophoresis, Gel, Two-Dimensional↗

PubMed1998

Stimulation of cholesterol release from rabbit foam cells by the action of a new inhibitor for acyl CoA:cholesterol acyltransferase (ACAT), HL-004.

A new inhibitor of acyl CoA:cholesterol acyltransferase (ACAT), HL-004 [N-(2, 6-diisopropylphenyl)tetradecylthioacetamide], suppressed the synthesis of cholesterol [14C]oleate at 10(-9) approximately 10(-7) M in a concentration-dependent manner in both THP-1 cell-derived macrophages and foam cells prepared from aortic intima of rabbits fed a high cholesterol diet. Incorporation of [3H]cholesterol oleate-beta very low density lipoproteins was not inhibited by HL-004 at 10(-9) approximately 10(-7) M. Release of radioactivity from the cells loaded with [3H]cholesterol oleate-beta very low density lipoproteins was increased by the inhibition of ACAT activity with HL-004. HL-004 did not affect on acid and neutral cholesterol esterases. As a result, cholesterol ester content in foam cells decreased. These data suggested that HL-004 decreases cholesterol ester in foam cells by increasing the release of cholesterol and therefore might suppress atherosclerotic lesions.

Acetanilides↗

PubMed1984

Monocytic origin of foam cells in human atherosclerotic plaques.

Foam cells in 4 human atherosclerotic plaques reacted with 3 rat monoclonal antibodies directed against T.200 ('anti-leucocyte common' antibody), HLA-Class II molecules and macrophage cytoplasm, respectively. Smooth muscle cells did not react. The results support the view that foam cells are monocyte-derived macrophages.

Adult↗

PubMedDate not supplied

[Electron-autoradiographic and biochemical study of the role of foam cells in low density lipoprotein metabolism].

Participation of foam cells in metabolism of lipoproteins of low density (LPLD) was studied by biochemical methods and by electronic autoradiography. The foam cells were isolated from atherosclerotic rabbit aorta after perfusion with 12I-LPLD within 6 hrs. Metabolic activity of foam cells was evaluated by the ratio of radioactivity in lipid and protein components of cells as well as by distribution of reduced argentum granules among the subcellular structures on autoradiogram. The biochemical studies showed that the lipid components of LPLD were preferably accumulated in foam cells. Electronic-autoradiography demonstrated that protein from the lipoprotein particles was also distributed intracellularly in various cytoplasmic structures. Foam cells appear to capture intact lipoprotein particles by pinocytosis with subsequent splitting of protein component by cellular lysosome apparatus.

Animals↗

PubMed2001

Stimulation of smooth muscle cell proliferation by ox-LDL- and acetyl LDL-induced macrophage-derived foam cells.

To test the hypothesis that LDL lacking of initial oxidation may also anticipate an essential role in the progression for atherosclerotic lesions, we studied the in vitro effect of foam cells induced by low density lipoprotein (LDL), oxidized (ox)-LDL or acetyl-LDL on smooth muscle cell (SMC) proliferation. Intraperitoneal macrophages collected from ICR mice were incubated with buffered saline LDL, ox-LDL or acetyl-LDL to induce foam cell formation. Porcine aortas with atherosclerotic lesions were collected from 5 pigs fed high cholesterol diets. The results indicate that foam cells induced by ox-LDL and acetyl-LDL, but not by LDL, promoted SMC proliferation. SMC proliferation was also increased by ruptured, ox-LDL- and acetyl-LDL- induced foam cells. Immunohistochemically, epitopes of the LDL, ox-LDL, and malondialdelyde (MDA)-LDL were present in atherosclerotic lesions, but the acetyl epitope was not. We suggest that foam cells, whether induced by the oxidized or acetyl or acetyl (unoxidized) form, play an essential role in the pathogenesis of atherosclerosis by stimulating SMC proliferation.

Animals↗

PubMed2006

Insulin and glucose play a role in foam cell formation and function.

BACKGROUND: Foam cell formation in diabetic patients often occurs in the presence of high insulin and glucose levels. To test whether hyperinsulinemic hyperglycemic conditions affect foam cell differentiation, we examined gene expression, cytokine production, and Akt phosphorylation in human monocyte-derived macrophages incubated with two types of oxidized low density lipoprotein (LDL), minimally modified LDL (mmLDL) and extensively oxidized LDL (OxLDL). METHODS AND RESULTS: Using Affymetrix GeneChip arrays, we found that several genes directly related to insulin signaling were changed. The insulin receptor and glucose-6-phosphate dehydrogenase were upregulated by mmLDL and OxLDL, whereas insulin-induced gene 1 was significantly down-regulated. In hyperinsulinemic hyperglycemic conditions, modified LDL upregulated Akt phosphorylation and expression of the insulin-regulated aminopeptidase. The level of proinflammatory cytokines, IL-lbeta, IL-12, and IL-6, and of a 5-lipoxygenase eicosanoid, 5-hydroxyeicosatetraenoic acid (5-HETE), was also increased. CONCLUSION: These results suggest that the exposure of macrophages to modified low density lipoproteins in hyperglycemic hyperinsulinemic conditions affects insulin signaling and promotes the release of proinflammatory stimuli, such as cytokines and eicosanoids. These in turn may contribute to the development of insulin resistance.

Cell Differentiation↗

PubMed1997

Characteristics of macrophage-derived foam cells isolated from atherosclerotic lesions of rabbits.

It is generally accepted that the foam cells in atherosclerotic lesions are derived mainly from monocytes/macrophages. We investigated whether the macrophage-derived foam cells, isolated from the atherosclerotic lesions of cholesterol-fed rabbits, would exhibit properties similar to those of blood monocytes in vitro and whether the cholesterol concentration of the macrophage-derived foam cells would decrease in the presence of an appropriate cholesterol acceptor in culture. We found that most (> 98%) of the foam cells isolated from atherosclerotic lesions were positive for anti-monocyte-macrophage antibody and nonspecific esterase. While almost all (> 98%) of the foam cells exhibited NaF-resistant, nonspecific esterase activity, the blood monocytes exhibited no such activity. Macrophage-derived foam cells contained larger amounts of cholesterol, most of it esterified, than the blood monocytes. Although blood monocytes exhibited a substantial amount of lysozyme, the freshly isolated, macrophage-derived foam cells showed no detectable lysozyme activity. The production of superoxide by macrophage-derived foam cells stimulated by PMA or opsonized zymosan was lower than that of stimulated monocytes. The cholesterol concentration of macrophage-derived foam cells decreased during five days of culture in the presence of an appropriate acceptor, such as normal and hypercholesterolemic rabbit serum and high density lipoprotein, although the rate of decrease was slow. Results suggest that macrophage-derived foam cells may be involved in both the progression and the regression of early atherosclerotic lesions.

Animals↗

PubMed1979

Ultrastructure of endometrial stromal foam cells.

An endometrium with cystic-glandular hyperplasia contained large foam cells in the stroma. The majority had ultrastructural characteristics of endometrial stromal cells, although a few were interpreted as macrophages. Endometrial stromal cells that appeared normal by light microscopy contained varying quantities of lipid on ultrastructural examination, and differed from the predominate type of foam cell only by having less cytoplasmic volume and maintaining an elongated shape. Cells intermediate in size and shape between normal stromal cells and foam cells further substantiated the origin of most of the foam cells from endometrial stroma.

Aged↗

PubMed1997

Role of activin-A and follistatin in foam cell formation of THP-1 macrophages.

Macrophage (M phi) foam cell formation is a characteristic event that occurs in the early stage of atherosclerosis. To examine the roles of activin-A, a member of the transforming growth factor-beta superfamily, and follistatin, the binding protein for activin-A, in M phi function, we investigated their effects on foam cell formation of THP-1 M phi s. When THP-1 M phi s were treated with activin-A (5 nmol/L), foam cell formation and cellular cholesteryl ester accumulation were decreased. This downregulation was paralleled by a reduction in cell association and degradation of acetylated LDL. The inhibitory effect of activin-A on cell association and degradation was dose dependent, and the effect was blocked by concomitant addition of follistatin. Activin-A (5 nmol/L) also decreased the Bmax for acetylated LDL and scavenger receptor mRNA expression. Follistatin showed an effect opposite to that of activin-A and promoted M phi foam cell formation and cellular cholesteryl ester accumulation. It increased binding, cell association, and degradation of acetylated LDL and upregulated scavenger receptor mRNA expression. Because follistatin is the binding protein for activin-A, follistatin's effect is considered to be mediated by blocking the inhibitory effect of intrinsic activin-A. These results indicate that activin-A inhibits and follistatin promotes M phi foam cell formation by regulating scavenger receptor mRNA expression. We conclude that activin-A and follistatin play important roles in the process of atherosclerosis by regulating M phi foam cell formation.

Activins↗

PubMed2002

Macrophage uptake of low-density lipoprotein bound to aggregated C-reactive protein: possible mechanism of foam-cell formation in atherosclerotic lesions.

Foam cells found in atherosclerotic lesions are believed to derive from macrophages that take up aggregated low-density lipoprotein (LDL) particles bound to the extracellular matrix of arterial walls. C-reactive protein (CRP) is an acute-phase protein found in atherosclerotic lesions, which when immobilized on a solid phase, can bind and cluster LDL particles in a calcium-dependent manner. In the present study, we examined whether CRP-bound aggregated LDL could be taken up by macrophages in culture. CRP molecules were aggregated in the presence of calcium and immobilized on the surface of polystyrene microtitre wells. Human LDL added to the wells bound to and aggregated on the immobilized CRP, also in a calcium-dependent manner. On incubation with macrophages, the immobilized CRP-bound LDL aggregates were readily taken up by the cells, as demonstrated by immunofluorescence microscopy, by the cellular accumulation of cholesterol and by the overexpression of adipophilin. Immunofluorescence microscopy and flow-cytometry analysis established that the uptake of the LDL-CRP complex was not mediated by the CRP receptor CD32. These observations with immobilized CRP and LDL, approximating the conditions that exist in the extracellular matrix of the arterial wall, thus suggest that CRP may contribute to the formation of foam cells in atherosclerotic lesions by causing the aggregation of LDL molecules that are then taken up by macrophages through a CD32-independent pathway.

Arteriosclerosis↗