Anti-Inflammatory Therapy for Atherosclerosis: Focusing on Cytokines

Poznyak, Anastasia V.; Bharadwaj, Dwaipayan; Prasad, Gauri; Grechko, Andrey V.; Sazonova, Margarita A.; Orekhov, Alexander N.

doi:10.3390/ijms22137061

Cited by 53 publications

(41 citation statements)

References 57 publications

(56 reference statements)

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“…In addition to the linkage between innate and adaptive immunity, IL-1β, IL6, and TNFα were found to induce acute and strong inflammatory responses, including leukocyte recruitment and proinflammatory mediator generation. These inflammatory responses cause excessive damage to peripheral tissues and then result in pathological diseases, such as atherosclerosis, adult respiratory distress syndrome, and tumours [30][31][32]. The levels of IL-1β, IL6, and TNFα in mRNA are upregulated by 1-NP in mouse lungs [33].…”

Section: Discussionmentioning

confidence: 99%

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Tsai

Chen

Liu

et al. 2021

Toxics

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Air pollution is a major environmental and public health problem worldwide. A nitro-polycyclic aromatic hydrocarbon and the most abundant air pollutant in diesel engine exhaust, 1-nitropyrene (1-NP), is caused by the incomplete combustion of carbonaceous organic substances. Macrophages are effector cells of the innate immune cells that provide resistance in the peripheral tissue. The overactivation of macrophages results in inflammation. The generation of proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor alpha, is induced by 1-NP in a concentration-dependent manner in macrophages. In this study, the production of proinflammatory mediators, such as nitrogen oxide and prostaglandin E2, was induced by 1-NP in a concentration-dependent manner through the expression of iNOS and COX2. The generation of proinflammatory cytokines, iNOS, and COX2 was induced by 1-NP through nuclear factor (NF)-κB p65 phosphorylation and the degradation of its upstream factor, IκB. Finally, Akt phosphorylation was induced by 1-NP in a concentration-dependent manner. These findings suggest that 1-NP exhibits a proinflammatory response through the NF-κB pathway activation due to Akt phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Tsai

Chen

Liu

et al. 2021

Toxics

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“…Mechanistically, inflammatory response mainly relies on various cytokines and mediators to participate in the whole process of atherosclerosis development. Especially in the late stage of atherosclerosis, pro-inflammatory cytokines cause abnormal functions of macrophages, endothelial cells, and lymphocytes, thus accelerating the destruction of plaques ( Poznyak et al, 2021 ). Cytokines are synthesized by various immune cells and secreted in autocrine and paracrine manners.…”

Section: Introductionmentioning

confidence: 99%

LKB1 Regulates Vascular Macrophage Functions in Atherosclerosis

et al. 2021

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Liver kinase B1 (LKB1) is known to shape the regulation of macrophage function by participating in multiple processes including cell metabolism, growth, and polarization. However, whether LKB1 also affects the functional plasticity of macrophages in atherosclerosis has not attracted much attention. Abnormal macrophage function is a pathophysiological hallmark of atherosclerosis, characterized by the formation of foam cells and the maintenance of vascular inflammation. Mounting evidence supports that LKB1 plays a vital role in the regulation of macrophage function in atherosclerosis, including affecting lipid metabolism reprogramming, inflammation, endoplasmic reticulum stress, and autophagy in macrophages. Thus, decreased expression of LKB1 in atherosclerosis aggravates vascular injury by inducing excessive lipid deposition in macrophages and the formation of foam cells. To systematically understand the role and potential mechanism of LKB1 in regulating macrophage functions in atherosclerosis, this review summarizes the relevant data in this regard, hoping to provide new ideas for the prevention and treatment of atherosclerosis.

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“…Given that H5% is a significant predictor of subclinical atherosclerosis in RA patients, we subsequently explored the potential roles of H5 in atherogenesis by using in vitro cell-based assay. Increasing evidence indicates that IL-1β and IL-8 are the key cytokine/chemokine in the atherogenesis [ 21 , 22 , 23 , 24 ]. We evaluated their expression levels of supernatants from H5- or H1-treated on THP-1 monocytes or THP-1-derived macrophages.…”

Section: Resultsmentioning

confidence: 99%

The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis

Chang

Cheng

Lung

et al. 2021

IJMS

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Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the percentage of the most electronegative subfraction of HDL-c (H5%) and RA-related atherosclerosis. Using anion-exchange purification/fast-protein liquid chromatography, we demonstrated significantly higher H5% in patients (median, 7.2%) than HC (2.8%, p < 0.005). Multivariable regression analysis revealed H5% as a significant predictor for subclinical atherosclerosis. We subsequently explored atherogenic role of H5 using cell-based assay. The results showed significantly higher levels of IL-1β and IL-8 mRNA in H5-treated (mean ± SD, 4.45 ± 1.22 folds, 6.02 ± 1.43-folds, respectively) than H1-treated monocytes (0.89 ± 0.18-folds, 1.03 ± 0.26-folds, respectively, both p < 0.001). In macrophages, H5 upregulated the mRNA and protein expression of IL-1β and IL-8 in a dose-dependent manner, and their expression levels were significantly higher than H1-treated macrophages (all p < 0.001). H5 induced more foam cell formation compared with H1-treated macrophages (p < 0.005). In addition, H5 has significantly lower cholesterol efflux capacity than H1 (p < 0.005). The results of nanoLC-MS/MS approach reveal that the best discriminator between high-H5% and normal-H5% is Apo(a), the main constituent of Lp(a). Moreover, Lp(a) level is a significant predictor for high-H5%. These observations suggest that H5 is involved in RA-related atherosclerosis.

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Anti-Inflammatory Therapy for Atherosclerosis: Focusing on Cytokines

Cited by 53 publications

References 57 publications

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

Proinflammatory Responses of 1-Nitropyrene against RAW264.7 Macrophages through Akt Phosphorylation and NF-κB Pathways

LKB1 Regulates Vascular Macrophage Functions in Atherosclerosis

The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis

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