scholarly journals A Chlamydia pneumoniae Component That Induces Macrophage Foam Cell Formation Is Chlamydial Lipopolysaccharide

1998 ◽  
Vol 66 (11) ◽  
pp. 5067-5072 ◽  
Author(s):  
Murat V. Kalayoglu ◽  
Gerald I. Byrne
Keyword(s):  
Cholesteryl Ester ◽  
Chlamydia Pneumoniae ◽  
Elevated Temperatures ◽  
Foam Cell ◽  
Cell Formation ◽  
Disease Process ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

ABSTRACT 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.

Leptin modulates ACAT1 expression and cholesterol efflux from human macrophages

2009 ◽  
Vol 297 (2) ◽  
pp. E474-E482 ◽  
Author(s):  
Shigeki Hongo ◽  
Takuya Watanabe ◽  
Shigeko Arita ◽  
Tomoko Kanome ◽  
Haruaki Kageyama ◽  
...  
Keyword(s):  
Cholesteryl Ester ◽  
Cholesterol Efflux ◽  
Leptin Receptor ◽  
Foam Cell ◽  
Cell Formation ◽  
Human Monocyte ◽  
Foam Cell Formation ◽  
Monocytic Differentiation ◽  
Macrophage Foam Cell ◽  
Cholesteryl Ester Accumulation

Leptin is an adipose tissue-derived hormone implicated in atherosclerosis and macrophage foam cell formation. The current study was conducted to examine the effect of leptin on cholesteryl ester accumulation in human monocytes/macrophages. Exogenously added leptin at 5 nM during differentiation of monocytes into macrophages for 7 days accelerated acetylated LDL (acetyl-LDL)-induced cholesteryl ester accumulation by 30–50%. Leptin did not affect endocytic uptake of acetyl-LDL; however, it increased ACAT activity 1.8-fold and ACAT-1 protein expression 1.9-fold. Among the four ACAT-1 mRNA transcripts, two shorter transcripts (2.8 and 3.6 kb) were upregulated ∼1.7-fold upon leptin treatment. The enhanced expression of ACAT-1 protein by leptin was suppressed by inhibitors of Janus-activated kinase2 (JAK2) and phosphatidylinositol 3-kinase (PI3K). HDL-mediated cholesterol efflux was suppressed by leptin, which was canceled by K-604, an ACAT-1 inhibitor. Expression of long form of leptin receptor was upregulated during monocytic differentiation into macrophages and sustained after differentiation. Thus, the results suggest that leptin accelerates cholesteryl ester accumulation in human monocyte-derived macrophages by increasing ACAT-1 expression via JAK2 and PI3K, thereby suppressing cholesterol efflux.

Impact of Salusin-α and -β on Human Macrophage Foam Cell Formation and Coronary Atherosclerosis

Circulation ◽  
2008 ◽  
Vol 117 (5) ◽  
pp. 638-648 ◽  
Author(s):  
Takuya Watanabe ◽  
Kae Nishio ◽  
Tomoko Kanome ◽  
Taka-aki Matsuyama ◽  
Shinji Koba ◽  
...  
Keyword(s):  
Coronary Atherosclerosis ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Macrophage Foam Cell

scholarly journals High-capacity selective uptake of cholesteryl ester from native LDL during macrophage foam cell formation

2012 ◽  
Vol 53 (10) ◽  
pp. 2081-2091 ◽  
Author(s):  
Jason M. Meyer ◽  
Ailing Ji ◽  
Lei Cai ◽  
Deneys R. van der Westhuyzen
Keyword(s):  
Cholesteryl Ester ◽  
Foam Cell ◽  
Cell Formation ◽  
High Capacity ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Selective Uptake

Tamoxifen inhibits macrophage FABP4 expression through the combined effects of the GR and PPARγ pathways

2013 ◽  
Vol 454 (3) ◽  
pp. 467-477 ◽  
Author(s):  
Meixiu Jiang ◽  
Ling Zhang ◽  
Xingzhe Ma ◽  
Wenquan Hu ◽  
Yuanli Chen ◽  
...  
Keyword(s):  
Protein Expression ◽  
Promoter Activity ◽  
Foam Cell ◽  
Regulatory Element ◽  
Cell Formation ◽  
Disease Process ◽  
Foam Cell Formation ◽  
Combined Effects ◽  
Macrophage Foam Cell ◽  
Fatty Acid Binding

Macrophage adipocyte fatty acid-binding protein (FABP4) plays an important role in foam cell formation and development of atherosclerosis. Tamoxifen inhibits this disease process. In the present study, we determined whether the anti-atherogenic property of tamoxifen was related to its inhibition of macrophage FABP4 expression. We initially observed that tamoxifen inhibited macrophage/foam cell formation, but the inhibition was attenuated when FABP4 expression was selectively inhibited by siRNA. We then observed that tamoxifen and 4-hydroxytamoxifen inhibited FABP4 protein expression in primary macrophages isolated from both the male and female wild-type mice, suggesting that the inhibition is sex-independent. Tamoxifen and 4-hydroxytamoxifen inhibited macrophage FABP4 protein expression induced either by activation of GR (glucocorticoid receptor) or PPARγ (peroxisome-proliferator-activated receptor γ). Associated with the decreased protein expression, Fabp4 mRNA expression and promoter activity were also inhibited by tamoxifen and 4-hydroxytamoxifen, indicating transcriptional regulation. Analysis of promoter activity and EMSA/ChIP assays indicated that tamoxifen and 4-hydroxytamoxifen activated the nGRE (negative glucocorticoid regulatory element), but inhibited the PPRE (PPARγ regulatory element) in the Fabp4 gene. In vivo, administration of tamoxifen to ApoE (apolipoprotein E)-deficient (apoE−/−) mice on a high-fat diet decreased FABP4 expression in macrophages and adipose tissues as well as circulating FABP4 levels. Tamoxifen also inhibited FABP4 protein expression by human blood monocyte-derived macrophages. Taken together, the results of the present study show that tamoxifen inhibited FABP4 expression through the combined effects of GR and PPARγ signalling pathways. Our findings suggest that the inhibition of macrophage FABP4 expression can be attributed to the anti-atherogenic properties of tamoxifen.

scholarly journals Salusins: Potential Use as a Biomarker for Atherosclerotic Cardiovascular Diseases

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kengo Sato ◽  
Rena Watanabe ◽  
Fumiko Itoh ◽  
Masayoshi Shichiri ◽  
Takuya Watanabe
Keyword(s):  
Cardiovascular Diseases ◽  
Vascular Tissue ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Human Macrophage ◽  
Central Administration ◽  
Macrophage Foam Cell ◽  
Atherosclerotic Cardiovascular Diseases

Human salusin-αand salusin-βare related peptides produced from prosalusin. Bolus injection of salusin-βinto rats induces more profound hypotension and bradycardia than salusin-α. Central administration of salusin-βincreases blood pressure via release of norepinephrine and arginine-vasopressin. Circulating levels of salusin-αand salusin-βare lower in patients with essential hypertension. Salusin-βexerts more potent mitogenic effects on human vascular smooth muscle cells (VSMCs) and fibroblasts than salusin-α. Salusin-βaccelerates inflammatory responses in human endothelial cells and monocyte-endothelial adhesion. Human macrophage foam cell formation is stimulated by salusin-βbut suppressed by salusin-α. Chronic salusin-βinfusion into apolipoprotein E-deficient mice enhances atherosclerotic lesions; salusin-αinfusion reduces lesions. Salusin-βis expressed in proliferative neointimal lesions of porcine coronary arteries after stenting. Salusin-αand salusin-βimmunoreactivity have been detected in human coronary atherosclerotic plaques, with dominance of salusin-βin macrophage foam cells, VSMCs, and fibroblasts. Circulating salusin-βlevels increase and salusin-αlevels decrease in patients with coronary artery disease. These findings suggest that salusin-βand salusin-αmay contribute to proatherogenesis and antiatherogenesis, respectively. Increased salusin-βand/or decreased salusin-αlevels in circulating blood and vascular tissue are closely linked with atherosclerosis. Salusin-αand salusin-βcould be candidate biomarkers and therapeutic targets for atherosclerotic cardiovascular diseases.

scholarly journals Chlamydia pneumoniae-Induced Macrophage Foam Cell Formation Is Mediated by Toll-Like Receptor 2

2006 ◽  
Vol 75 (2) ◽  
pp. 753-759 ◽  
Author(s):  
Fei Cao ◽  
Antonio Castrillo ◽  
Peter Tontonoz ◽  
Fabio Re ◽  
Gerald I. Byrne
Keyword(s):  
Chlamydia Pneumoniae ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Toll Like Receptor ◽  
Macrophage Foam Cell ◽  
E Coli ◽  
Toll Like Receptor 2 ◽  
Ce Content

ABSTRACT 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 Pam3-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.

Abstract 126: Chlamydia Pneumoniae Induces Foam Cell Formation Of Macrophages By Activating The TLR4/TRIF/IRF3 Pathway

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Shuang Chen ◽  
Rosalinda Sorrentino ◽  
Kenichi Shimada ◽  
Timothy Crother ◽  
Moshe Arditi
Keyword(s):  
Transcriptional Control ◽  
Chlamydia Pneumoniae ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Peritoneal Macrophages ◽  
Foam Cell Formation ◽  
Toll Like Receptors ◽  
Macrophage Foam Cell

Background: Chlamydia pneumoniae (CP) induces macrophage foam cell formation (FCF), a key event in early atherosclerosis, in the presence of low-density lipoprotein (LDL). Recent studies have indicated the role of Toll-Like Receptors in atherogenesis. Liver X receptors (LXR) are nuclear receptors that play central roles in the transcriptional control of lipid metabolism and determinants of atherosclerosis. Induction of LXR-activated genes has also been shown to influence the pathogen pattern recognition activity of the Toll-like receptors 3 and 4 (TLR3/4). The TLR and the LXR pathways converge on the transcription factor IRF3. Objective: We hypothesized that TLR and the LXR and IRF3 pathways participate in CP infection mediated FCF and acceleration of atherosclerosis, and that the MyD88- independent pathway via TLR4/TRIF and IRF3 play a role in this acceleration. Methods: Peritoneal macrophages were isolated from C57BL/6 wild type (WT) mice, IRF3 −/− mice, TLR4 −/− mice and TRIF −/− mice. Cells were treated with UV killed CP (UVCP, 5x10 5 IFU) with or without ox-LDL (100 μg/ml) in the presence or absence of LXR agonist GW3965 (2nM). LPS (10 ng/ml) and PolyI:C (1μg/ml) were used as positive controls as TLR4 and TLR3 ligands, respectively. FCF was examined by Oil Red O staining. The percentages of foam cells in total macrophages were quantified. Results : FCF was significantly reduced in IRF3−/− cells compared with WT cells stimulated with UVCP plus ox-LDL. Foam cells induced by LPS with ox-LDL were also significantly reduced in IRF3−/− cells compared to WT cells (p<0.05). Furthermore, the synthetic LXR agonist GW3965 significantly diminished CP induced FCF in WT cells. FCF was significantly reduced in TLR4−/− and TRIF−/− macrophages compared to WT cells when stimulated with UVCP with ox-LDL (p<0.05). Conclusion : Chlamydia pneumoniae infection can activate the TLR4/TRIF/IRF3 pathway and does play an important role in CP- mediated foam cell formation in macrophages. Therefore, infections such as the one caused by CP, can trigger the TLR4/TRIF/IRF3 pathway leading to the down regulation of LXRs and shifting of cholesterol transport toward pro-foam cell production and thereby accelerating atherogenesis.. Supported by NIH grants AI 067995 and HL66436 to MA.

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