Familial forms of isolated hypercholesterolemia are inherited autosomal-dominantly and are caused by defects of the low-density lipoprotein (LDL) receptor protein or its ligand, the apolipoprotein B-100, the exclusive apolipoprotein moiety of the LDL particles. Mutations at the LDL receptor gene locus (more than 150 different mutations have been described up to now) lead to familial hypercholesterolemia (FH); the only mutation at the apolipoprotein B-100 gene locus described in detail so far leads to the so-called familial defective apolipoprotein B-100 (FDB).
Glucosamine, commonly consumed for the treatment of osteoarthritis, is classified as a nutritional supplement; however, there are few data regarding its metabolic or vascular effects. Glucosamine is a component of the hexosamine pathway, which has been implicated in the development of insulin resistance. Anecdotal reports suggest that glucosamine consumption can increase circulating cholesterol concentrations.
ACAT2, the enzyme responsible for the formation of cholesteryl esters incorporated into apolipoprotein B-containing lipoproteins by the small intestine and liver, forms predominantly cholesteryl oleate from acyl-CoA and free cholesterol. The accumulation of cholesteryl oleate in plasma lipoproteins has been found to be predictive of atherosclerosis. Accordingly, a method was developed in which fatty acyl-CoA subspecies could be extracted from mouse liver and quantified.
Arteriosclerosis, Thrombosis, and Vascular Biology
OBJECTIVES: The enzyme acyl-coenzymeA (CoA):cholesterol O-acyltransferase 2 (ACAT2) in the liver synthesizes cholesteryl esters (CE) from cholesterol and fatty acyl-CoA, which get incorporated into apoB-containing lipoproteins that are secreted into the bloodstream. Dietary fatty acid composition influences the amount and fatty acid composition of CE within apoB-containing lipoproteins.
We tested the hypothesis that dietary supplementation with echium oil (EO), which is enriched in stearidonic acid (SDA; 18:4 n-3), the product of Delta-6 desaturation of 18:3 n-3, will decrease plasma triglyceride (TG) concentrations and result in conversion of SDA to eicosapentaenoic acid (EPA) in the liver.
BACKGROUND: Vascular inflammation and lipid deposition are prominent features of atherosclerotic lesion formation. We have shown previously that the dithiol compound alpha-lipoic acid (LA) exerts antiinflammatory effects by inhibiting tumor necrosis factor-alpha- and lipopolysaccharide-induced endothelial and monocyte activation in vitro and lipopolysaccharide-induced acute inflammatory responses in vivo.
The Journal of Neuroscience: The Official Journal of the Society for Neuroscience
Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate beta-amyloid (Abeta). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk.
The Journal of Pharmacology and Experimental Therapeutics
Liver X receptor (LXR) agonists have the potential to treat atherosclerosis based on their ability to enhance reverse cholesterol transport. However, their side effects, such as induction of liver lipogenesis and triglyceridemia, may limit their pharmaceutical development.
The 3'untranslated region (UTR) of human LDL receptor (LDLR) mRNA contains three AU-rich elements (AREs) responsible for rapid mRNA turnover and mediates the stabilization induced by berberine (BBR). However, the identities of the specific RNA binding proteins involved in the regulation of LDLR mRNA stability at the steady state level or upon BBR treatment are unknown.
PCSK9 is a natural inhibitor of LDL receptor (LDLR) that binds the extracellular domain of LDLR and triggers its intracellular degradation. PCSK9 and LDLR are coordinately regulated at the transcriptional level by sterols through their promoter-imbedded sterol response elements (SRE) and co-induced by statins. Identification of regulatory networks modulating PCSK9 transcription is important for developing selective repressors of PCSK9 to improve statin efficacy by prolonging the up-regulation of LDLR.