Treatment of Vulnerable Plaques: Current and Future Strategies
Levon Michael Khachigian in High-Risk Atherosclerotic Plaques, 2004
Clearance of cholesterol from LDL and HDL by the liver is relevant to this process and involves the selective uptake of cholesteryl ester by SRB-1180 and the excretion of biliary sterols by the expression of ABCG5 and ABCG8.181 SRB-1 is also likely to play a role in facilitating cholesterol mobilization from peripheral stores.182 Although over-expression of SRB-1 lowers plasma HDLc, its role in mediating net clearance of cholesterol from tissues is supported by accelerated atherosclerosis with cardiac ischemia in mice deficient in SRB-1.183 Because several key components of the reverse cholesterol transport pathway are regulated by ligands for LXR and RXR, these may be suitable targets for future therapies, and there is some indication they can be modulated by PPAR ligands.
Medicinal Mushrooms
Anil K. Sharma, Raj K. Keservani, Surya Prakash Gautam in Herbal Product Development, 2020
More than 380 species of mushrooms have been documented to possess medicinal properties and this as a result of their high content of prebiotics (Geurts et al., 2014). Mushrooms prebiotics are known to improve the antioxidant status as a result of alterations in the composition of gut microbiota. Mushrooms play a vital role in immune response during the treatment of respiratory diseases, atherosclerosis, cancer, and other metabolic diseases (Koyyalamudi et al., 2009a, 2009b; Varshney et al., 2013). Prebiotics from mushrooms also have hypocholesterolemia properties that help reduce lipogenic gene expression (Hmgcr, Fasn, Srebp1c, and Acaca) and genes responsible for reverse cholesterol transport (Abcg5 and Abcg8) significantly, as well as an increase in Low Density Lipoprotein Receptor gene expression in the liver (Meneses et al., 2016). Ganoderma lucidium is a mushroom that has been documented to reduce obesity in mice by altering the composition of gut microbiota (Xu and Zhang, 2015).
Effects of physical activity on the gallbladder and biliary tract in health and disease
Roy J. Shephard in Physical Activity and the Abdominal Viscera, 2017
Studies in mice bred for their susceptibility to gallbladder disease have shown that training also increases the hepatic expression of two genes (LDLr and SRB1) that are known to be involved in the clearance of cholesterol. Exercised mice demonstrate an up-regulation of the protein Cyp27 that is associated with the hepatic production of bile acids.[83] The net effect of exercise upon the intestinal reabsorption of cholesterol remains less clear. Trained animals show a reduced expression of NPC1L1 (which would reduce cholesterol reabsorption), but at the same time there is a reduction in the expression of ABCG5 and G8 (which would have the effect of increasing cholesterol resorption).[83]
Administration timing and duration-dependent effects of sesamin isomers on lipid metabolism in rats
Published in Chronobiology International, 2020
Norifumi Tateishi, Satoshi Morita, Izumi Yamazaki, Hitoshi Okumura, Masaru Kominami, Sota Akazawa, Ayuta Funaki, Namino Tomimori, Tomohiro Rogi, Hiroshi Shibata, Shigenobu Shibata
In the present study, gene expression of Abcg5 and Abcg8, which are involved in the excretion of cholesterol from the liver, was significantly promoted by the administration of SE. There was no conclusive evidence of administration timing-dependency about this effect, although SE was slightly stronger with administration at the beginning of the active phase. Regarding the regulation of Abcg5 and Abcg8, we know that circadian rhythmicity peaks in the light phase and that they are under the control of clock genes (Molusky et al. 2018; Pan et al. 2016). It is also known that they are target genes of the transcription factor LXRα and that they are induced to respond to cholesterol spikes (Calkin and Tontonoz 2012). In the present study, we observed that SE did not affect the gene expression of Lxra. Further research is needed to confirm the underlying mechanism for the promotion of Abcg5 and Abcg8 by SE or the possibility of interaction with SE and LXRα.
Beyond the Usual Suspects: Expanding on Mutations and Detection for Familial Hypercholesterolemia
Published in Expert Review of Molecular Diagnostics, 2021
Shirin Ibrahim, Joep C. Defesche, John J.P. Kastelein
Variants in the genes encoding adenosine triphosphate-binding cassette transporters G5 and G8 (ABCG5 and ABCG8) have also been shown to affect LDL-C levels. ABCG5 and ABCG8 form a heterodimer that is responsible for the transmembrane transport of sterols, in particular, plant sterols [41]. In the intestine, the complex is involved in the transport of sterols from the enterocyte into the intestinal lumen, whereas in the liver it promotes the transport of sterols into the bile. Mutations in ABCG5 and ABCG8 can cause sitosterolemia, an autosomal recessive disorder whereby plant sterols accumulate in blood and tissues. Studies have shown an association between hypercholesterolemia and sitosterolemia in the general population [41]. With the expansion of NGS panels in FH patients, variants in ABCG5 and ABCG8 have been frequently discovered. Patients with sitosterolemia can present with xanthomas and premature CAD, characteristics that closely mimic the clinical FH phenotype [56]. Studies by Tada et al. and Nomura et al. suggest that heterozygous pathogenic variants in the ABCG5/ABCG8 can worsen the clinical expression of FH in terms of additional elevation of LDL-C levels and cardiovascular risk [57,58]. Recently, we have also addressed this issue and could not confirm these findings [41].
Alterations of drug-metabolizing enzymes and transporters under diabetic conditions: what is the potential clinical significance?
Published in Drug Metabolism Reviews, 2018
Feng Chen, De-Yi Li, Bo Zhang, Jie-Yu Sun, Fang Sun, Xing Ji, Jin-Chun Qiu, Robert B. Parker, S. Casey Laizure, Jing Xu
Located on the apical membrane of enterocytes and hepatocytes, ABCG5 and ABCG8 limit intestinal absorption and facilitate biliary secretion of cholesterol and phytosterols. This heterodimer transporter is positively regulated by Liver X receptor. Mutated ABCG5/G8 genes could cause sitosterolemia (abnormal accumulation of cholesterol and plant sterols in the circulation), thereby leading to premature cardiovascular disease (Yu et al. 2014). The hepatic mRNA expression of ABCG5/G8 was decreased in SI rats with declined cholesterol output (Bloks et al. 2004), but increased in SI mice (Aleksunes et al. 2013). Both mRNA and protein expression of ABCG5/G8 in jejunum of the SI rats were found to be suppressed, whist campesterol and β-sitosterol concentrations in rat plasma were decreased (Bloks et al. 2004).