Molecular mechanism of curcumin on the suppression of cholesterol accumulation in macrophage foam cells and atherosclerosis

2012 ◽  
Vol 56 (5) ◽  
pp. 691-701 ◽  
Author(s):  
Jing-Feng Zhao ◽  
Li-Chieh Ching ◽  
Yu-Chu Huang ◽  
Chien-Yu Chen ◽  
An-Na Chiang ◽  
...  
Keyword(s):  
Molecular Mechanism ◽  
Foam Cells ◽  
Cholesterol Accumulation ◽  
Macrophage Foam Cells

Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages

2018 ◽  
Vol 46 (01) ◽  
pp. 87-106 ◽  
Author(s):  
Hung-Chih Lin ◽  
Chong-Kuei Lii ◽  
Hui-Chun Chen ◽  
Ai-Hsuan Lin ◽  
Ya-Chen Yang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Cholesterol Accumulation ◽  
Macrophage Foam Cell ◽  
Macrophage Foam Cells ◽  
Mrna And Protein Expression ◽  
Anti Inflammatory

oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent atherosclerosis.

scholarly journals Interplay of Autophagy Inducer Rapamycin and Proteasome Inhibitor MG132 in Reduction of Foam Cell Formation and Inflammatory Cytokine Expression

2018 ◽  
Vol 27 (8) ◽  
pp. 1235-1248
Author(s):  
Wei Zhang ◽  
Wan Xu ◽  
Wenli Chen ◽  
Quan Zhou
Keyword(s):  
Molecular Mechanism ◽  
Proteasome Inhibitor ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Oxidative Modification ◽  
Raw 264.7 Cells ◽  
Foam Cell Formation ◽  
Proteasome Inhibitor Mg132 ◽  
Macrophage Foam Cells

MG132 is a pivotal inhibitor of the ubiquitin-proteasome system (UPS), and rapamycin (RAPA) is an important inducer of autophagy. MG132 and RAPA have been shown to be effective agents that can cure multiple autoimmune diseases by reducing inflammation. Although individual MG132 and RAPA showed protective effects for atherosclerosis (AS), the combined effect of these two drugs and its molecular mechanism are still unclear. In this article we investigate the regulation of oxidative modification of low-density lipoprotein (ox-LDL) stress and foam cell formation in the presence of both proteasome inhibitor MG132 and the autophagy inducer RAPA to uncover the molecular mechanism underlying this process. We established the foam cells model by ox-LDL and an animal model. Then, we tested six experimental groups of MG132, RAPA, and 3MA drugs. As a result, RAPA-induced autophagy reduces accumulation of polyubiquitinated proteins and apoptosis of foam cells. The combination of MG132 with RAPA not only suppressed expression of the inflammatory cytokines and formation of macrophage foam cells, but also significantly affected the NF-κB signaling pathway and the polarization of RAW 264.7 cells. These data suggest that the combination of proteasome inhibitor and autophagy inducer ameliorates the inflammatory response and reduces the formation of macrophage foam cells during development of AS. Our research provides a new way to suppress vascular inflammation and stabilize plaques of late atherosclerosis.

Macrophage foam cells and atherosclerosis

10.2741/kruth ◽  
2001 ◽  
Vol 6 (1) ◽  
pp. d429 ◽  
Author(s):  
Howard, S. Kruth
Keyword(s):  
Foam Cells ◽  
Macrophage Foam Cells

scholarly journals Lysosomal accumulation of unesterified cholesterol in model macrophage foam cells

1993 ◽  
Vol 268 (13) ◽  
pp. 9653-9660
Author(s):  
R.K. Tangirala ◽  
F.H. Mahlberg ◽  
J.M. Glick ◽  
W.G. Jerome ◽  
G.H. Rothblat
Keyword(s):  
Foam Cells ◽  
Unesterified Cholesterol ◽  
Macrophage Foam Cells ◽  
Lysosomal Accumulation
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