Epigallocatechin-3-gallate Reduces Scavenger Receptor A Expression and Foam Cell Formation in Human Macrophages

Abstract

Foam cells are formed when macrophages imbibe low-density lipoprotein (LDL) through scavenger receptors. Here we examined how epigallocatechin-3-gallate (EGCG) influences foam cell formation. We found that EGCG dose-dependently reduced oxidized LDL (oxLDL) uptake in THP-1 (10 μM, 20.0 ± 0.50, p < 0.05) and primary macrophages (134.6 ± 15.6, p < 0.05) and reduced intracellular cholesterol content in these cells, respectively (10 μM, 32.6 ± 0.14, p < 0.05; 31.7 ± 1.26, p < 0.05). EGCG treatment decreased scavenger receptor A expression, but not the expression of CD36 or of reverse cholesterol transporters. Moreover, EGCG stimulated translocation of the p50 and p65 subunits of NF-κB and enhanced NF-κB DNA-binding activity, thus suppressing SR-A promoter activity. EGCG's suppression of SR-A expression was blocked by the NF-κB inhibitor Bay. The present findings suggest that EGCG regulates NF-κB activity and thus suppresses SR-A expression, oxLDL uptake, and foam cell formation.

Oligomeric proanthocyanidins and epigallocatechin gallate aggravate autophagy of foam cells through the activation of Class III PI3K/Beclin1‐complex mediated cholesterol efflux

“…The formation of foam cells induced by OxLDL is a well‐accepted model as it stimulates the growth of macrophages, upregulated the expression of scavenger receptors such as SR‐A1, SR‐B1, LOX‐1, CD‐36, and CD‐68 . In agreement with our results, a previous study demonstrated that treatment with EGCG reduced the OxLDL uptake by macrophages and prevented the formation of foam cells through the downregulated the expression of SR‐A1 scavenger receptor …”

“…18 In agreement with our results, a previous study demonstrated that treatment with EGCG reduced the OxLDL uptake by macrophages and prevented the formation of foam cells through the downregulated the expression of SR-A1 scavenger receptor. 5 A previous study on C57BL/6 mice fed with high-fat diet showed reduced autophagy through attenuation of autophagic/lysosomal compartment, impaired lysosomal acidification, and hydrolase activity due to excessive chronic lipid accumulation. 19 In addition to this, OxLDL mediated inhibition of foam cell autophagy upregulated the expression of p62 which leads to an autophagy-deficient condition.…”

“…A monomer epigallocatechin gallate (EGCG) present in OPC showed potent antioxidant, antiinflammatory, and antiatherogenic properties. 5 Previous reports from our laboratory emphasized that, OPC exerts potent antioxidant and anti-inflammatory properties against ISO induced myocardial infarction. 6 In this study, we hypothesize that treatment with OPC and EGCG reestablish the impaired cholesterol efflux mechanism by activating Class III phosphoinositide 3 kinase (Class III PI3K)/Beclin1 signaling pathway with selective inhibition of Class I phosphoinositide 3 kinase (Class I PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in foam cells.…”

“…Two to tenunits of catechins and epicatechins are predominantly present in the complex structure of oligomeric proanthocyanidins (OPC). A monomer epigallocatechin gallate (EGCG) present in OPC showed potent antioxidant, anti‐inflammatory, and antiatherogenic properties . Previous reports from our laboratory emphasized that, OPC exerts potent antioxidant and anti‐inflammatory properties against ISO induced myocardial infarction .…”

The Use of Nutraceuticals to Counteract Atherosclerosis: The Role of the Notch Pathway

“…In macrophage cell lines, catechins also mediate suppression of expression of metalloproteinase-9 (MMP-9), monocyte chemoattractant protein-1 MCP-1, and Toll-like receptor 4 (TLR4), which have a major role in atherosclerosis [79]. Moreover, in macrophages, epigallocatechin-3-gallate (EGCG) suppresses oxLDL uptake and foam cell formation [80]. In ApoE -/mice, catechin consumption has been associated with reduced susceptibility of LDL to oxidation and aggregation and thus to the reduced atherosclerotic lesion area [81].…”