Macrophages and Atherosclerosis

Newby, Andrew C.

doi:10.1007/978-3-7091-0338-8_17

Cited by 2 publications

(4 citation statements)

References 95 publications

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“…Macrophages are believed to possess a pivotal function in lipid-laden foam cell formation and inflammation during atherosclerosis progression and plaque destabilization [ 9 , 10 ]. It is well known that macrophages can be activated by lipopolysaccharide (LPS) to uptake oxidized low-density lipoprotein (ox-LDL), which is a necessary step for macrophage foam cell production and the subsequent fatty streak formation.…”

Section: Introductionmentioning

confidence: 99%

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease

Feng

Deng

et al. 2014

Lipids Health Dis

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BackgroundAtherosclerosis constitutes the leading contributor to morbidity and mortality in cardiovascular and cerebrovascular diseases. Lipid deposition and inflammatory response are the crucial triggers for the development of atherosclerosis. Recently, microRNAs (miRNAs) have drawn more attention due to their prominent function on inflammatory process and lipid accumulation in cardiovascular and cerebrovascular disease. Here, we investigated the involvement of miR-21 in lipopolysaccharide (LPS)-induced lipid accumulation and inflammatory response in macrophages.MethodsAfter stimulation with the indicated times and doses of LPS, miR-21 mRNA levels were analyzed by Quantitative real-time PCR. Following transfection with miR-21 or anti-miR-21 inhibitor, lipid deposition and foam cell formation was detected by high-performance liquid chromatography (HPLC) and Oil-red O staining. Furthermore, the inflammatory cytokines interleukin 6 (IL-6) and interleukin 10 (IL-10) were evaluated by Enzyme-linked immunosorbent assay (ELISA) assay. The underlying molecular mechanism was also investigated.ResultsIn this study, LPS induced miR-21 expression in macrophages in a time- and dose-dependent manner. Further analysis confirmed that overexpression of miR-21 by transfection with miR-21 mimics notably attenuated lipid accumulation and lipid-laden foam cell formation in LPS-stimulated macrophages, which was reversely up-regulated when silencing miR-21 expression via anti-miR-21 inhibitor transfection, indicating a reverse regulator of miR-21 in LPS-induced foam cell formation. Further mechanism assays suggested that miR-21 regulated lipid accumulation by Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) pathway as pretreatment with anti-TLR4 antibody or a specific inhibitor of NF-κB (PDTC) strikingly dampened miR-21 silence-induced lipid deposition. Additionally, overexpression of miR-21 significantly abrogated the inflammatory cytokines secretion of IL-6 and increased IL-10 levels, the corresponding changes were also observed when silencing miR-21 expression, which was impeded by preconditioning with TLR4 antibody or PDTC.ConclusionsTaken together, these results corroborated that miR-21 could negatively regulate LPS-induced lipid accumulation and inflammatory responses in macrophages by the TLR4-NF-κB pathway. Accordingly, our research will provide a prominent insight into how miR-21 reversely abrogates bacterial infection-induced pathological processes of atherosclerosis, indicating a promising therapeutic prospect for the prevention and treatment of atherosclerosis by miR-21 overexpression.

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Section: Introductionmentioning

confidence: 99%

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease

Feng

Deng

et al. 2014

Lipids Health Dis

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“…Atherosclerosis begins with the transmigration of oxidized LDLs to the intima (the subendothelial space) which cause injuries to endothelial cells. The injury is described as cellular damage and one result of this type of damage is the loss of function of the cell [ 4 , 7 , 8 ]. Endothelial cells respond to the injury by becoming sticky which alerts the macrophages to ingest the oxidized LDLs.…”

Section: Introductionmentioning

confidence: 99%

“…Endothelial cells respond to the injury by becoming sticky which alerts the macrophages to ingest the oxidized LDLs. These macrophages are then overloaded with oxidized LDLs; the appearance of the lipids in the macrophages gives them a foamy appearance; hence they are given the name “foam cells.” The accumulation of foam cells leads to the formation of fatty streaks [ 7 ]. After some time atheroma takes place, the smooth muscle cells migrate and further restrict the blood flow leading to atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

“…Complex lesions occur with the advancement of inflammatory responses, necrotic core formation, and death of foam cells. Finally, thrombosis occurs when fibrous caps rupture [ 4 , 7 – 9 ]. 3-Hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) is the rate limiting factor for the formation of mevalonate in the cholesterol biosynthesis pathway.…”

Section: Introductionmentioning

confidence: 99%

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Crude Ethanol Extract of Pithecellobium ellipticum as a Potential Lipid‐Lowering Treatment for Hypercholesterolaemia

Wong

Wijaya

Ting

et al. 2014

Evidence-Based Complementary and Alternative Medicine

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If left untreated, hypercholesterolaemia can lead to atherosclerosis, given time. Plants from the Fabaceae family have shown the ability to significantly suppress atherosclerosis progression. We selected four extracts from Pithecellobium ellipticum, from the Fabaceae family, to be screened in a 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase) assay. The ethanol extract, at a concentration of 500 μg/mL, exhibited superior inhibition properties over the other extracts by demonstrating 80.9% inhibition, while 0.223 μg/mL of pravastatin (control) showed 78.1% inhibition towards enzymatic activity. These findings led to the fractionation of the ethanol extract using ethyl acetate : methanol (95 : 5), gradually increasing polarity and produced seven fractions (1A to 7A). Fraction 7A at 150 μg/mL emerged as being the most promising bioactive fraction with 78.7% inhibition. FRAP, beta carotene, and DPPH assays supported the findings from the ethanol extract as it exhibited good overall antioxidant activity. The antioxidant properties have been said to reduce free radicals that are able to oxidize lipoproteins which are the cause of atherosclerosis. Phytochemical screenings revealed the presence of terpenoid, steroid, flavonoid, and phenolic compounds as the responsible group of compound(s), working individually or synergistically, within the extract to prevent binding of HMG-CoA to HMG-CoA reductase.

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Macrophages and Atherosclerosis

Cited by 2 publications

References 95 publications

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease

miR-21 attenuates lipopolysaccharide-induced lipid accumulation and inflammatory response: potential role in cerebrovascular disease

Crude Ethanol Extract of Pithecellobium ellipticum as a Potential Lipid‐Lowering Treatment for Hypercholesterolaemia

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