The Experts below are selected from a list of 22650 Experts worldwide ranked by ideXlab platform
Gerald I. Byrne - One of the best experts on this subject based on the ideXlab platform.
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chlamydia pneumoniae induced macrophage Foam Cell formation is mediated by toll like receptor 2
Infection and Immunity, 2007Co-Authors: Fei Cao, Antonio Castrillo, Peter Tontonoz, Gerald I. ByrneAbstract:Chlamydia pneumoniae induces macrophage Foam Cell formation, a hallmark of early atherosclerosis, in the presence of low-density lipoprotein (LDL). This study examined the role that Toll-like receptor 2 (TLR2) and TLR4 may play in pathogen-induced Foam Cell formation. Murine macrophage RAW 264.7 Cells either infected with C. pneumoniae or treated with the TLR4 ligand E. coli lipopolysaccharide (LPS) or the TLR2 ligand Pam(3)-Cys-Ala-Gly-OH (Pam) became Oil Red O-stained Foam Cells and showed increased cholesteryl ester (CE) content when cocultured with LDL. In macrophages from TLR2(-/-) mice, Foam Cells were induced by Escherichia coli LPS but not by C. pneumoniae or Pam. Conversely, C. pneumoniae or Pam, but not E. coli LPS, induced Foam Cells in the TLR4-deficient GG2EE macrophage Cell line, suggesting that C. pneumoniae elicits Foam Cell formation predominantly via TLR2. Enhancing cholesterol efflux using the liver X receptor (LXR) agonist GW3965 significantly decreased the CE content of Cells exposed to each of the three TLR ligands (C. pneumoniae, Pam, and E. coli LPS). Overall, our results suggest that activation of the LXR signaling pathway may affect potentially atherogenic processes modulated by the TLR ligands.
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A Chlamydia pneumoniae Component That Induces Macrophage Foam Cell Formation Is Chlamydial Lipopolysaccharide
Infection and immunity, 1998Co-Authors: Murat V. Kalayoglu, Gerald I. ByrneAbstract:Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage Foam Cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced Foam Cell formation in the murine macrophage Cell line RAW-264.7. Infected RAW Cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage Foam Cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and Foam Cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage Foam Cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.
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induction of macrophage Foam Cell formation by chlamydia pneumoniae
The Journal of Infectious Diseases, 1998Co-Authors: Murat V. Kalayoglu, Gerald I. ByrneAbstract:Foam Cell formation is the hallmark of early atherosclerosis. It was found that the intraCellular bacterium Chlamydia pneumoniae induces Foam Cell formation by human monocyte-derived macrophages. Exposure of macrophages to C. pneumoniae followed by low-density lipoprotein (LDL) caused a marked increase in the number of Foam Cells and accumulation of cholesteryl esters. Foam Cell formation was not inhibited by the antioxidant butylated hydroxytoluene nor fucoidan, suggesting that lipid accumulation did not involve scavenger receptors. In contrast, addition of heparin, which blocks binding of LDL to the LDL receptor, inhibited C. pneumoniae-induced Foam Cell formation, suggesting that the pathogen induced lipid accumulation by dysregulating native LDL uptake or metabolism (or both). These data demonstrate that an infectious agent can induce macrophage Foam Cell formation and implicate C. pneumoniae as a causative factor in atherosclerosis.
Motoaki Shichiri - One of the best experts on this subject based on the ideXlab platform.
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human β migrating very low density lipoprotein induces Foam Cell formation in human mesangial Cells
Atherosclerosis, 1997Co-Authors: Yoshichika Anami, Shozo Kobori, Masakazu Sakai, Masaya Kasho, Takeshi Nishikawa, Toshihiro Yano, Hirofumi Matsuda, Takeshi Matsumura, Toru Takemura, Motoaki ShichiriAbstract: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.
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β migrating very low density lipoproteins induce Foam Cell formation in mouse mesangial Cells
Atherosclerosis, 1995Co-Authors: Takeshi Nishikawa, Yoshichika Anami, Shozo Kobori, Masaya Kasho, Toshihiro Yano, Haruo Takeda, Takayuki Higashi, Yoshihiro Sato, Takayuki Sasahara, Motoaki ShichiriAbstract:Abstract To elucidate whether β-migrating very low density lipoproteins (β-VLDL) induce Foam Cell formation in mesangial Cells or not, surface binding and Foam Cell formation with β-VLDL were studied in mouse mesangial Cells. Specific binding kinetics for β-VLDL and low density lipoproteins (LDL) on the mesangial Cells were observed with K d = 3.8 and 13.7 μg / ml , and B max = 65.9 and 71.9 ng / mg Cell protein at 4 °C, respectively. The binding of β-VLDL was inhibited by excess amounts of LDL or β-VLDL, but not by acetyl-low density lipoproteins. Ligand blotting using β-VLDL or LDL and immunoblotting using anti-human LDL receptor monoclonal antibody detected the same apparent single protein (approx. 130 kDa). Incorporation of [ 14 C]oleate into cholesteryl ester in mouse mesangial Cells was enhanced by β-VLDL to 3-fold higher than that by LDL, and it was inhibited by chloroquine or anti-human LDL receptor monoclonal antibody. The light microscopic findings also demonstrated that cholesteryl ester deposition increased in these Cells incubated with β-VLDL, but not with LDL. In conclusion, β-VLDL was specifically taken up by receptor-mediated endocytosis in mouse mesangial Cells through LDL receptors, resulting in Foam Cell formation.
Murat V. Kalayoglu - One of the best experts on this subject based on the ideXlab platform.
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A Chlamydia pneumoniae Component That Induces Macrophage Foam Cell Formation Is Chlamydial Lipopolysaccharide
Infection and immunity, 1998Co-Authors: Murat V. Kalayoglu, Gerald I. ByrneAbstract:Chlamydia pneumoniae infection is associated with atherosclerotic heart and vessel disease, but a causal relationship between this pathogen and the disease process has not been established. Recently, it was reported that C. pneumoniae induces human macrophage Foam Cell formation, a key event in early atheroma development, suggesting a role for the organism in atherogenesis. This study further examines C. pneumoniae-induced Foam Cell formation in the murine macrophage Cell line RAW-264.7. Infected RAW Cells accumulated cholesteryl esters when cultured in the presence of low-density lipoprotein in a manner similar to that described for human macrophages. Exposure of C. pneumoniae elementary bodies to periodate, but not elevated temperatures, inhibited cholesteryl ester accumulation, suggesting a role for chlamydial lipopolysaccharide (cLPS) in macrophage Foam Cell formation. Purified cLPS was found to be sufficient to induce cholesteryl ester accumulation and Foam Cell formation. Furthermore, the LPS antagonist lipid X inhibited C. pneumoniae and cLPS-induced lipid uptake. These data indicate that cLPS is a C. pneumoniae component that induces macrophage Foam Cell formation and suggest that infected macrophages chronically exposed to cLPS may accumulate excess cholesterol to contribute to atheroma development.
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induction of macrophage Foam Cell formation by chlamydia pneumoniae
The Journal of Infectious Diseases, 1998Co-Authors: Murat V. Kalayoglu, Gerald I. ByrneAbstract:Foam Cell formation is the hallmark of early atherosclerosis. It was found that the intraCellular bacterium Chlamydia pneumoniae induces Foam Cell formation by human monocyte-derived macrophages. Exposure of macrophages to C. pneumoniae followed by low-density lipoprotein (LDL) caused a marked increase in the number of Foam Cells and accumulation of cholesteryl esters. Foam Cell formation was not inhibited by the antioxidant butylated hydroxytoluene nor fucoidan, suggesting that lipid accumulation did not involve scavenger receptors. In contrast, addition of heparin, which blocks binding of LDL to the LDL receptor, inhibited C. pneumoniae-induced Foam Cell formation, suggesting that the pathogen induced lipid accumulation by dysregulating native LDL uptake or metabolism (or both). These data demonstrate that an infectious agent can induce macrophage Foam Cell formation and implicate C. pneumoniae as a causative factor in atherosclerosis.
Gordon A Francis - One of the best experts on this subject based on the ideXlab platform.
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low lal lysosomal acid lipase expression by smooth muscle Cells relative to macrophages as a mechanism for arterial Foam Cell formation
Arteriosclerosis Thrombosis and Vascular Biology, 2021Co-Authors: Joshua A Dubland, Ying Wang, Sima Allahverdian, Katrina J Besler, Carleena Ortega, Collin S Pryma, Kamel Boukais, Teddy Chan, Michael A Seidman, Gordon A FrancisAbstract:Objective We previously reported smooth muscle Cells (SMCs) represent ≥50% of Foam Cells in human coronary and ≈70% in apoE (apolipoprotein E)-deficient mouse aortic atheromas and exhibit reduced expression of the cholesterol exporter ABCA1 (ATP-binding cassette transporter A1). A major stimulus for ABCA1 expression is flux of cholesterol out of lysosomes, generated by hydrolysis of lipoprotein cholesteryl esters by LAL (lysosomal acid lipase). In this study, we investigated the potential role lysosomal dysfunction might play in Foam Cell formation by arterial SMCs. Approach and Results: Human monocyte-derived macrophages (macrophages) and arterial SMCs were treated with aggregated LDL (low-density lipoprotein) to increase intraCellular cholesterol and investigated for lysosomal and postlysosomal cholesterol metabolism defects. Human and mouse atheromas were analyzed for LAL expression. Unlike macrophages, aggregated LDL uptake failed to upregulate ABCA1 expression, downregulate new cholesterol synthesis, or to significantly increase 27-hydroxycholesterol levels in SMCs. Confocal microscopy revealed retention of neutral lipids within lysosomal compartments in SMCs, while macrophages showed most lipids as cytosolic droplets. LIPA mRNA levels and LAL protein were markedly reduced in SMCs. Treatment of SMCs with medium containing LAL resulted in significantly reduced lysosomal lipid accumulation and increased cholesterol efflux to apoA-I (apolipoprotein AI). Human and mouse atheromas exhibited low LAL/Lipa expression in intimal SMCs when compared with intimal macrophages. Conclusions These findings indicate the inherently low level of LAL in SMCs compared with macrophages is associated with reduced capacity to catabolize atherogenic lipoproteins and is a mechanism for SMC Foam Cell formation in atherosclerosis.
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contribution of monocyte derived macrophages and smooth muscle Cells to arterial Foam Cell formation
Cardiovascular Research, 2012Co-Authors: Sima Allahverdian, Parveer S Pannu, Gordon A FrancisAbstract:Smooth muscle Cells (SMCs) are the main Cell type in intimal thickenings and some stages of human atherosclerosis. Like monocyte-derived macrophages, SMCs accumulate excess lipids and contribute to the total intimal Foam Cell population. In contrast, apolipoprotein (Apo)E-deficient and LDL receptor-deficient mice develop atherosclerotic lesions that are macrophage- as opposed to SMC-rich. The lesser contribution of SMCs to lesion development in these mouse models has distracted attention away from the importance of SMC cholesterol homeostasis in the artery wall. Intimal SMCs accumulate excess amounts of cholesteryl esters when compared with medial layer SMCs, possibly explained by reduced ATP-binding cassette transporter A1 expression and ApoA-I binding to intimal-type SMCs. The aim of this review is to compare the relative contribution of monocyte-derived macrophages and SMCs to human vs. mouse atherosclerosis, and describe what is known about lipid uptake and removal mechanisms contributing to arterial macrophage and SMC Foam Cell formation. An increased understanding of the contribution of these Cell types to lesion development will help to delineate their relative importance in atherogenesis and as potential therapeutic targets.
Takeshi Nishikawa - One of the best experts on this subject based on the ideXlab platform.
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human β migrating very low density lipoprotein induces Foam Cell formation in human mesangial Cells
Atherosclerosis, 1997Co-Authors: Yoshichika Anami, Shozo Kobori, Masakazu Sakai, Masaya Kasho, Takeshi Nishikawa, Toshihiro Yano, Hirofumi Matsuda, Takeshi Matsumura, Toru Takemura, Motoaki ShichiriAbstract: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.
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β migrating very low density lipoproteins induce Foam Cell formation in mouse mesangial Cells
Atherosclerosis, 1995Co-Authors: Takeshi Nishikawa, Yoshichika Anami, Shozo Kobori, Masaya Kasho, Toshihiro Yano, Haruo Takeda, Takayuki Higashi, Yoshihiro Sato, Takayuki Sasahara, Motoaki ShichiriAbstract:Abstract To elucidate whether β-migrating very low density lipoproteins (β-VLDL) induce Foam Cell formation in mesangial Cells or not, surface binding and Foam Cell formation with β-VLDL were studied in mouse mesangial Cells. Specific binding kinetics for β-VLDL and low density lipoproteins (LDL) on the mesangial Cells were observed with K d = 3.8 and 13.7 μg / ml , and B max = 65.9 and 71.9 ng / mg Cell protein at 4 °C, respectively. The binding of β-VLDL was inhibited by excess amounts of LDL or β-VLDL, but not by acetyl-low density lipoproteins. Ligand blotting using β-VLDL or LDL and immunoblotting using anti-human LDL receptor monoclonal antibody detected the same apparent single protein (approx. 130 kDa). Incorporation of [ 14 C]oleate into cholesteryl ester in mouse mesangial Cells was enhanced by β-VLDL to 3-fold higher than that by LDL, and it was inhibited by chloroquine or anti-human LDL receptor monoclonal antibody. The light microscopic findings also demonstrated that cholesteryl ester deposition increased in these Cells incubated with β-VLDL, but not with LDL. In conclusion, β-VLDL was specifically taken up by receptor-mediated endocytosis in mouse mesangial Cells through LDL receptors, resulting in Foam Cell formation.