Effects of selenium on SePP and Apo B-100 Gene expressions in human primary hepatocytes
Robert Hofstra, Noriyuki Koibuchi, Suthat Fucharoen in Advances in Biomolecular Medicine, 2017
Cholesterol in the blood is mainly carried by Low-Density Lipoprotein (LDL) and most significantly associated with atherosclerotic plaque formation (Gouni-Berthold and Sachinidis, 2004). Apolipoprotein B (apo B) is correlated with LDL particles, a study by Dhingra and Bansal, 2005 demonstrated that in mice, selenium deficiency caused increased of apo B expression during experimental hypercholesterolemia and Selenium supplementation leads to down-regulation of apo B expression (Dhingra and Bansal, 2005). Apolipoprotein B 100 (apo B-100) is apo B that is consists of the ligand-binding domain for binding of LDL to LDL-R site (Segrest et al., 2001). Several studies proposed that apoB-100 levels might be a better indicator than total or LDL cholesterol levels for measuring the concentration of atherogenic lipoprotein particles (Davidson, 2012) because most of the studies demonstrated that one molecule of apo B-100 exists per lipoprotein particle, hence the quantity of apo B-100 in fasting plasma predicts the sum of LDL and VLDL particles (Vega and Grundy, 1990, Harper and Jacobson, 2010). Based on this facts, there was lacking data for the efficacy of selenium supplementation for suppressing Apo B-100 in the healthy human.
Molecular Imaging of Atherosclerosis with Magnetic Resonance
Michel M. J. Modo, Jeff W. M. Bulte in Molecular and Cellular MR Imaging, 2007
Low-density lipoprotein (LDL) and high-density lipoprotein (HDL) are endogenous lipid nanoparticles that play an important role in the transport of cholesterol. These nanoparticles consist of a lipid core of cholesterol esters and triglycerides covered by a phospholipid monolayer that contains a large apolipoprotein.68 The apolipoprotein B-100 (ApoB-100, 550 kDa) associated with LDL contains one or more clusters of cationic amino acids that naturally target LDL receptors (LDLRs) on cells. Uptake of LDL is via endocytosis, with subsequent uptake into cellular lysosomes that degrade the material. All LDL receptors are recycled so that many LDL particles may be accumulated within a given cell. LDL receptors are found on several normal tissue types (liver, adrenal glands, ovaries, etc.); however, macrophages in atherosclerotic plaques and some tumoral cells overexpress LDLR.69,70 As a result, lanthanide-labeled LDL may be used as natural targets for atherosclerotic plaques and other cells that overexpress LDLR.34,71–78 Specifically, recent studies have shown that manganese-mesoporphyrin-(MnMeso) labeled LDL may allow both the detection of atherosclerotic plaque and the assessment of lipoprotein kinetics in the vessel wall.78
Lipid Subfraction Testing
Stephen T. Sinatra, Mark C. Houston in Nutritional and Integrative Strategies in Cardiovascular Medicine, 2015
All the high-risk atherogenic lipoproteins (VLDL, IDL [intermediate-density lipoprotein], LDL, and Lp(a)) have in common the presence of one molecule of apolipoprotein B. Apolipoprotein B levels (apoB) and the LDL particle number (LDL-P) currently represent two available tests that accurately provide a direct measurement of atherogenic particles31 and are superior to the traditionally measured LDL cholesterol level (LDL-C).
Heightened risks of cardiovascular disease in South Asian populations: causes and consequences
Published in Expert Review of Cardiovascular Therapy, 2023
Maria Stefil, Jack Bell, Peter Calvert, Gregory YH Lip
Lipoprotein(a) comprises an LDL particle with apolipoprotein B covalently bound to apolipoprotein(a). Serum lipoprotein(a) levels associate linearly with atherosclerotic ASCVD risk, and as lipoprotein(a) levels are highly genetically determined, they have garnered attention in explaining racial differences in ASCVD risk. Studies to date have had mixed results regarding whether lipoprotein(a) levels are disproportionately elevated in South Asian populations. In the largest study to date, lipoprotein(a) levels from 460,506 individuals registered with the UK biobank were compared between ethnic groups. This study confirmed that lipoprotein(a) levels vary by race with the Black population having the highest median values followed by South Asian, white and Chinese groups (median values 75, 31, 19 and 16 nmol/L, respectively). However, despite this variation in median lipoprotein(a) levels, the risk for atherosclerotic ASCVD per 50 nmol/L increase in lipoprotein(a) appeared similar across ethnic groups[85]. It is important that trials assessing lipoprotein(a)-lowering interventions, such as antisense oligonucleotides, ensure that different ethnic groups are well represented[86].
Homozygous familial hypercholesterolemia and its treatment by inclisiran
Published in Expert Opinion on Orphan Drugs, 2020
A David Marais, Dirk J Blom, Frederick J Raal
The bulk of the cholesterol circulating in the blood plasma is in low-density lipoprotein (LDL) in which apolipoprotein B100 (apoB100) is practically the only protein. In the liver, apoB100 accepts triglyceride and cholesterol ester from microsomal triacylglycerol transfer protein (MTP) and the particle is secreted as very low-density lipoprotein (VLDL). In the circulation, the triglyceride contained in VLDL undergoes hydrolysis by lipoprotein lipase retained on the vascular endothelium of muscle, adipose tissue, and lactating breast tissue. Ultimately, hydrolysis of remnants by hepatic lipase yields smaller, cholesterol-rich LDL particles. Only once LDL is formed will apoB100 bind the LDL receptor on cells expressing the cognate receptors in response to intracellular depletion of cholesterol. The first description of a familial pattern of hypercholesterolemia, tendon xanthomata, and premature ischemic heart disease was published in 1938 [4]. Many years later the molecular pathophysiology of FH was proven to be due to the impaired uptake of LDL owing to defects in the LDL receptor. Brown and Goldstein were awarded the Nobel Prize for this work [5].
Colesevelam – a bile acid sequestrant for treating hypercholesterolemia and improving hyperglycemia
Published in Expert Opinion on Pharmacotherapy, 2022
Oluwayemisi Esan, Adie Viljoen, Anthony S. Wierzbicki
Cardiovascular disease (CVD) is one of the leading causes of morbidity and mortality. A substantial component is caused by lipids with associations shown with total cholesterol and its easily measured subfractions low-density lipoprotein-cholesterol (LDL-C) [1] and high-density lipoprotein-cholesterol (HDL-C) [2]. Non-high density lipoprotein cholesterol (nHDL-C [2]; which adds the contribution of triglyceride (TG)-rich lipoproteins; (TGRLs) [3,4] to LDL-C is a better predictor of CVD than LDL-C alone. Studies also find a strong association of CVD with apolipoprotein B100 levels. As there is one molecule of apoB per very low density lipoprotein (VLDL) or LDL particle this translates to an association with the cholesterol content of nHDL-C particles . Statins and other LDL-C reducing drugs reduce the 5 year incidence of major coronary events, coronary revascularisation and stroke by about 21% per 1 mmol/L reduction in LDL-C [5]. Treatment options beyond statins are only considered as add-on treatment, when these drugs are not tolerated or when hypertriglyceridemia is present. Bile acid sequestrants (BAS) are one of the classes of traditional lipid-lowering therapies now viewed as third line agents for reducing LDL-C. This article reviews the mechanism of action, pharmacokinetics, pharmacodynamics, safety and efficacy of the BAS colesevelam in CVD and patients with type 2 diabetes (T2DM) focusing on their effects on glycemic control. Other reviews have addressed the role of colesevelam in reducing LDL-C [6,7]
Related Knowledge Centers
- Chylomicron
- Protein
- Cardiovascular Disease
- Apolipoprotein
- Gene
- Very Low-Density Lipoprotein
- Lipoprotein(A)
- Intermediate-Density Lipoprotein
- Low-Density Lipoprotein
- Cholesterol