Innate Immune System in Cardiovascular Diseases
Shyam S. Bansal in Immune Cells, Inflammation, and Cardiovascular Diseases, 2022
Macrophages in atherosclerotic plaques are predominantly derived from circulating monocytes [90]. In murine models, hypercholesterolemia promotes selective expansion of classical monocytes through CSF1- and IL-3-dependent extramedullary hematopoiesis [90]. In humans, classical CD14high CD16low monocytes are increased in hyper-cholesterolemia [91]. Subendothelial retention of low-density lipoprotein (LDL) and local production of CCL2, CCL20, and sphingosine-1-phosphate recruit monocytes to the site of arterial inflammation [92, 93]. Suppression of monocyte recruitment led to plaque regression [94]. Myeloid-specific depletion of ATP-binding cassette transporters (ABCA1 and ABCG1), which are important in the efflux of LDL to high-density lipoprotein (HDL), led to increased atherosclerosis and monocytosis [95].
Inorganic Chemical Pollutants
William J. Rea, Kalpana D. Patel in Reversibility of Chronic Disease and Hypersensitivity, Volume 4, 2017
Genetically engineered disruption of cholesterol metabolism defines the two major models of atherosclerosis; apolipoprotein E-deficient (ApoE+) and LDL receptor (LDLR)-deficient mice develop two ApoE and other mice deficient in lipid-efflux proteins, such as the adenosine triphosphate (ATP)-binding cassette transporter 1 (ABCA1) and ATP-binding cassette transporter 1 (ABCAA1) and ATP-binding cassette subfamily G member 1 (ABCG1), have forged a mechanistic link between leukocyte and lipid biology. Trapped cholesterol in hematopoietic stem and progenitor cells (HSPCs) that lack the crucial cholesterol efflux machinery leads to the expression of the granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 common beta chain receptor on the plasma membrane contributes to excessive proliferation.247,248 In other words, cholesterol efflux suppress proliferation. Concurrently, lipid-rich splenic phagocytes release IL-23, which induces a cascade that eventually liberates HSPCs from their medullary niches.249 When HSPCs seed extramedullary sites, they encounter GM-CSF and IL-3.250 The net effect is HSPC proliferation, extramedullary hematopoiesis, leukocytosis, and accelerated atherosclerosis.
Nutrition and Nutritional Supplements in the Management of Dyslipidemia and Dyslipidemia-Induced Cardiovascular Disease
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2022
The plant sterols are also anti-inflammatory and decrease the levels of proinflammatory cytokines such as interleukins (IL-6, IL1b) and TNF-α, as well as hsCRP, LpPLA 2, and fibrinogen; however, these effects vary among the various phytosterols [135]. Other potential mechanisms include modulation of signaling pathways, activation of cellular stress responses, cellular growth arrest, reduction of Apo-B48 secretion from intestinal and hepatic cells, reduction of cholesterol synthesis with suppression of HMG-CoA reductase and cytochrome P 450 (CYP7A1), interference with SREBP, and promotion of RCT via ABCA1 and ABCG1 [135]. The biological activity of phytosterols is both cell-type and sterol-specific [133].
Exome-chip meta-analysis identifies association between variation in ANKRD26 and platelet aggregation
Published in Platelets, 2019
Ming-Huei Chen, Lisa R. Yanek, Joshua D. Backman, John D. Eicher, Jennifer E. Huffman, Yoav Ben-Shlomo, Andrew D. Beswick, Laura M. Yerges-Armstrong, Alan R. Shuldiner, Jeffrey R. O’Connell, Rasika A. Mathias, Diane M. Becker, Lewis C. Becker, Joshua P. Lewis, Andrew D. Johnson, Nauder Faraday
ABCG1 encodes an ATP-binding cassette (ABC) transporter known to be involved in cellular efflux of high density lipoprotein, suppression of toll-like receptor mediated inflammation, and atherosclerosis [29]. ABC transporters are also known to regulate maturation of hematopoietic progenitor cells and MKs [29]; however, an association with platelet aggregation has not been reported. Although our gene-based meta-analysis suggested an association between genetic variation in ABCG1 and ADP-induced aggregation, PolyPhen and SIFT predicted both variants we identified to be benign. One of these variants—rs151254598—encoding a glycine to arginine substitution, was associated with a reduction in ADP-induced aggregation in CaPS similar in direction to the discovery cohort; however, we could not impute this rare SNV in CaPS with confidence. Thus, confirmation of this genotype-phenotype association requires additional replication.
Impact of DNA methylation on ADME gene expression, drug disposition, and efficacy
Published in Drug Metabolism Reviews, 2022
Xu Hao, Yuanyuan Li, Jialu Bian, Ying Zhang, Shiyu He, Feng Yu, Yufei Feng, Lin Huang
Higher ABCA1 cg14019050 methylation was correlated with lower ABCA1 gene expression in the ENCODE consortium has been reported by Ma et al. (Ma et al. 2016). The negative correlation between ABCB1 promoter methylation and gene expression has been proved in some cancer cell lines and MDR resistance models. The corresponding CpG sites are located downstream of TSS (+524, +526, +554, +556, +580, +583, +587) (Spitzwieser et al. 2016). Liu et al. found that ABCG1 gene expression was negatively correlated with ABCG1 methylation site cg06500161 in all nondiabetic participants in the Framingham Heart Study Offspring (Liu et al. 2020). Methylation bands were present but ABCG2 gene expression was not detected in SUN-C4, Colo201, LS174T, and SW480. And the CpG island region (−136 to −417) contains 21 CpG dinucleotide sites and is part of the promoter for the ABCG2 gene (Moon et al. 2016). The SLC5A8 transcriptional repression was associated with abnormal methylation of a 379-bp (+123 to +501) region, which contains 45 CpG sites (Hernandez-Juarez et al. 2019). Chen et al. confirmed that the significant down-regulation of OCT1 mRNA expression in hepatocellular carcinoma was explained by methylation of specific CpG sites, that is, cg13466809 and cg27292431 in the 5′-UTR and exon 1 of the SLC22A1 gene (Chen, Neul, et al. 2020).
Pharmacotherapy options in pulmonary alveolar proteinosis
Published in Expert Opinion on Pharmacotherapy, 2020
Sabina Antonela Antoniu, Ruxandra Rajnoveanu, Mihaela Grigore, Ileana Antohe
PPARγ expression was found to be significantly impaired in alveolar macrophages from patients with PAP, but was restored after treatment with exogenous GM-CSF [33–36]. PPARγ activation also results in upregulation of the transmembrane protein ABCG1, which is responsible for cholesterolphospholipid acid efflux from various cell types, including alveolar macrophages [37]. ABCG1 expression was found to be reduced both in patents with PAP and in GM-CSF knockout mice. Its activity was restored by corrective GM-CSF therapy, by ABCG1 lentivirus-based gene therapy, and also in vitro by exposing human alveolar macrophages from patients with PAP to rosiglitazone [38].
Related Knowledge Centers
- Phospholipid
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