Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

Yuan, Yuan; Li, Peng; Ye, Jing

doi:10.1007/s13238-012-2025-6

Cited by 152 publications

(109 citation statements)

References 73 publications

(75 reference statements)

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“…2A) and 20 differentially regulated KEGG pathways; LPS stimulation differences are indicated by PC1 ( Fig. 2A) macrophages and foam cells; however neonatal macrophages did not contain lipid residues [18,19]. Furthermore, a significant lack of F4/80 expression, reduced expressions of CD11b and CD14 was shown, whereas other markers of the myeloid lineage, such as CD68 were equally expressed.…”

Section: Discussionmentioning

confidence: 93%

Distinct phenotypic features of neonatal murine macrophages

et al. 2014

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Neonates rely on their innate immune system. Resident tissue macrophages are considered to be initiators and regulators of the innate immune response and thus, appear to be especially important to neonates. We hypothesized that the phenotype and function of neonatal tissue macrophages differ from their adult counterparts. Peritoneal macrophages from neonatal (<24 h) and adult (6 weeks old) C57BL/6J mice were isolated and analyzed by high-content chipcytometry. After stimulation for 6 h with LPS (0, 1, 10, 100 ng/mL), macrophage transcriptome was analyzed by microarray and cytokine release was measured using multiparametric bead assays. Antigen presenting capacity was compared by T-cell stimulation assays. We observed that neonatal murine peritoneal macrophages are characterized by selective lack of expression of F4/80, MHC class II, and costimulatory molecules (CD80, CD86). Furthermore, we found differences in the transcriptome between neonatal and adult macrophages, unstimulated and after LPS stimulation. Although neonatal macrophages showed a significantly increased secretion of proinflammatory cytokines upon LPS stimulation, their potential to induce T-cell proliferation was significantly reduced. In conclusion, we observed a distinct phenotype of the neonatal macrophage population. The specific functions of this macrophage population could help to understand the excessive inflammatory reactions observed in the very young.Keywords: Immune responses r Macrophages r Neonate immunity r Toll-like receptors (TLRs) Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionNeonates and in particular preterm infants are extremely vulnerable to states of inflammation [1]. They have an increased susceptibility to microbial infections with an enhanced morbidity and Correspondence: Mr. Thomas Winterberg e-mail: Winterberg.thomas@mh-hannover.de mortality [2]. Sepsis, pneumonia, and gastrointestinal disorders such as necrotizing enterocolitis are a common threat to patients in neonatal intensive care. The first days of life represent a period of transition of the immune system: The protection of the fetus by the maternal immune system and the sterile environment are lost and the newborn has to cope with the outside world and its multiple foreign antigens. Although maternal antibodies help the neonate in the first weeks, it has to develop its own adaptive immune capacities during infancy [2]. In the neonatal period, monocytes and [6][7][8][9]. Until now, neonatal monocytes and macrophages have been described as immature or dormant myeloid cells. However, these studies are based on peripheral blood monocytes or CBMs, which further differentiate into macrophages ex vivo. Little is known about tissue macrophages in neonates, due to technical difficulties of their isolation and evaluation, but a recent study demonstrated their unique function during heart tissue regeneration [10].It has been shown that the heterogeneous murine macrophage populations are orig...

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Section: Discussionmentioning

confidence: 93%

Distinct phenotypic features of neonatal murine macrophages

et al. 2014

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“…Moreover, these lipid-laden foam cells, present from the earliest discernable fatty streak lesions to advanced complicated lesions and plaque disruption, are key regulators of the pathological behavior of plaques [1][2][3][4][5]47) . Hence, reducing the formation of foam cells may be an efficient strategy for treating and preventing atherosclerosis 4) .…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, excessive lipid accumulation in macrophages of the arterial intima drives the secretion of proinflammatory mediators, potentiating atherogenesis 3) . Lipid homeostasis, particularly cholesterol homeostasis, is a critical step in the formation of macrophage foam cells 4,5) . Macrophage cholesterol homeostasis maintenance is generally thought to result from the balance between influx, endogenous synthesis/hydrolysis, and efflux.…”

Section: Introductionmentioning

confidence: 99%

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

Pang

Xiong

et al. 2015

J Atheroscler Thromb

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Aim: Macrophage foam cell formation is the most prominent characteristic of the early stages of atherosclerosis. Ubiquitin Fold Modifier 1 (UFM1) is a new member of the ubiquitin-like protein family, and its underlying mechanism of action in macrophage foam cell formation is poorly understood. Our current study focuses on UFM1 and investigates its role in macrophage foam cell formation. Methods: Using real-time quantitative PCR (qRT-PCR) and western blot analysis, we first analyzed the UFM1 expression in mouse peritoneal macrophages (MPMs) from ApoE / mice in vivo and in human macrophages treated with oxLDL in vitro. Subsequently, the effects of UFM1 on macrophages foam cell formation were determined by Nile Red staining and direct lipid analysis. We then examined whether UFM1 affects the process of lipid metabolism in macrophages. Lastly, with the method of small interfering RNA (siRNA), we delineated the mechanism of UFM1 to attenuate lipid accumulation in THP-1 macrophages. Results: UFM1 is dramatically upregulated under atherosclerosis conditions both in vivo and in vitro. Moreover, UFM1 markedly decreased macrophage foam cell formation. Mechanistic studies revealed that UFM1 increased the macrophage cholesterol efflux, which was due to the increased expression of ATP-binding cassette transporters A1 (ABCA1) and G1 (ABCG1). Furthermore, the upregulation of ABCA1 and ABCG1 by UFM1 resulted from liver X receptor (LXR ) activation, which was confirmed by the observation that LXR siRNA prevented the expression of ABCA1 and ABCG1. Consistent with this, the UFM1-mediated attenuation of lipid accumulation was abolished by such inhibition. Conclusions: Taken together, our results showed that UFM1 could suppress foam cell formation via the LXR -dependent pathway.

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“…The formation of foam cells within the arterial wall is thought to play a pivotal role in the development of atherosclerotic lesions (24). In the last decade, several studies have shown that in addition to macrophages, VSMCs accumulate excess intracellular cholesteryl (25,26) and give rise to a significant number of foam cells in atherosclerotic lesions (14,27).…”

Section: Discussionmentioning

confidence: 99%

17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway

Wang

Liu

Zhu

et al. 2014

International Journal of Molecular Medicine

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Abstract. Estrogen has pleiotropic effects on the cardiovascular diseases, yet the underlying mechanisms remain incompletely understood. Cholesterol efflux is a key mechanism through which to prevent foam cell formation and the development of atherosclerosis. Recent studies highlight the role of vascular smooth muscle cell (VSMC)-derived foam cells in atherogenesis. However, it remains unclear whether estrogen promotes cholesterol efflux from VSMCs and inhibits VSMC-derived foam cell formation. In the present study, we demonstrated that 17β-estradiol (E2) markedly enhanced cholesterol efflux to apolipoprotein (apo)A-1 and high-density lipoprotein (HDL) and attenuated oxidized low-density lipoprotein (ox-LDL) induced cholesteryl ester accumulation in VSMCs, which was associated with an increase in the expression of ATP-binding cassette transporters ABCA1 and ABCG1. The upregulation of ABCA1 and ABCG1 expression by E2 resulted from liver X receptor (LXR)α activation, which was confirmed by the prevention of the expression of ABCA1 and ABCG1 after inhibition of LXRα with a pharmacological inhibitor or small interfering RNA (siRNA). Furthermore, E2 increased LXRα, ABCA1 and ABCG1 expression in VSMCs via the estrogen receptor (ER), and the involvement of ERβ was confirmed by the use of selective ERα or ERβ antagonists (MPP and PHTPP) and agonists (PPT and DPN). These findings suggest that E2 promotes cholesterol efflux from VSMCs and reduces VSMCderived foam cell formation via ERβ-and LXRα-dependent upregulation of ABCA1 and ABCG1 and provide novel insights into the anti-atherogenic properties of estrogen.

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Lipid homeostasis and the formation of macrophage-derived foam cells in atherosclerosis

Abstract: ABSTRACT

Cited by 152 publications

References 73 publications

Distinct phenotypic features of neonatal murine macrophages

Distinct phenotypic features of neonatal murine macrophages

UFM1 Protects Macrophages from oxLDL-Induced Foam Cell Formation Through a Liver X Receptor α Dependent Pathway

17β-estradiol promotes cholesterol efflux from vascular smooth muscle cells through a liver X receptor α-dependent pathway

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