Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contrary to high plasma levels of low-density lipoprotein cholesterol (LDL-C), closely linked with coronary heart disease (CHD), high-density lipoprotein cholesterol (HDL-C) play an antiatherogenic role, through the reverse cholesterol transport from peripheral cells to the liver. New data in the pathophysiology of a rare genetic dyslipidemia, the Tangier disease, characterized by very low HDL-C levels and premature CHD, have shed light on this complex mechanism. In this disease, cholesterol efflux from peripheral cells is dramatically reduced, and this has been recently shown to be caused by mutations in an ATP-binding cassette transporter, which normally stimulates cholesterol efflux. Reverse cholesterol transport is therefore greatly decreased. Epidemiological data have revealed that 15% to 30% of coronary patients have low HDL-C levels. However, this is often combined with high triglycerides levels, and this association is frequently found in diabetic patients, especially prone to CHD. HDL-C has been repeatedly shown to be an inverse predictor of CHD. This has been enhanced by recent interventional studies (Veterans Affairs HDL Intervention Study, Bezafibrate Infarction Prevention Study) which have provided strong evidence that pharmacological increase of HDL-C, in combination with decrease in triglycerides level, reduces incidence of CHD.
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PMID:[Clinical, epidemiologic, and biochemical findings on the reverse cholesterol transport (cholesterol-HDL)]. 1147 68

Dietary fatty acids are known to play an important role in the development as well as prevention of dyslipidemia. In this study, we evaluated the impact of feeding polyunsaturated fatty acids (PUFAs) for a period of 4 months on various aspects of cholesterol metabolism in genetically obese mutant rats of WNIN/GR-Ob strain. Based on their phenotype, lean and obese rats were divided into two groups, A and B respectively, and further subdivided depending on the type of dietary fat. Control groups of rats (AI and BI), were fed on 4% groundnut oil, which was replaced by safflower oil; n-6 PUFA diet (AII and BII) or oil blend of safflower and soybean oil, n-6 and n-3 PUFA diet (AIII and BIII) in the experimental groups. It was observed that feeding of diets with n-6 PUFA or a combination of n-6 and n-3 PUFAs resulted in marked elevation of plasma levels of total as well as HDL cholesterol and triglycerides in obese rats (BII and BIII), as compared to the control group (BI). Further, plasma HDL fraction of obese rats had elevated apolipoprotein E (apo E), while apo A1 levels remained unaltered. Increased lecithin: cholesterol acyltransferase (LCAT) activity and cholesteryl ester (CE) levels in the plasma and enhanced expression of hepatic scavenger receptor class B type1 (SR-B1) were also observed in PUFA-fed obese rats (BII and BIII). However, there was no change in hepatic ATP-binding cassette transporter protein A1 (ABCA1) levels in the obese rats fed on PUFA rich diets. Intriguingly, though these changes favor efficient removal of cholesterol from peripheral tissues, its esterification and enhanced clearance through reverse cholesterol transport (RCT); plasma HDL-C remained higher in these genetically dyslipidemic obese rats, thereby pointing at yet unknown mechanisms, involved in cholesterol homeostasis, which need to be studied.
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PMID:Impact of feeding polyunsaturated fatty acids on cholesterol metabolism of dyslipidemic obese rats of WNIN/GR-Ob strain. 1884 26

Dyslipidemia is a commonly encountered clinical condition and is an important determinant of cardiovascular disease. Although secondary factors play a role in clinical expression, dyslipidemias have a strong genetic component. Familial hypercholesterolemia is usually due to loss-of-function mutations in LDLR, the gene coding for low density lipoprotein receptor and genes encoding for proteins that interact with the receptor: APOB, PCSK9 and LDLRAP1. Monogenic hypertriglyceridemia is the result of mutations in genes that regulate the metabolism of triglyceride rich lipoproteins (eg LPL, APOC2, APOA5, LMF1, GPIHBP1). Conversely familial hypobetalipoproteinemia is caused by inactivation of the PCSK9 gene which increases the number of LDL receptors and decreases plasma cholesterol. Mutations in the genes APOB, and ANGPTL3 and ANGPTL4 (that encode angiopoietin-like proteins which inhibit lipoprotein lipase activity) can further cause low levels of apoB containing lipoproteins. Abetalipoproteinemia and chylomicron retention disease are due to mutations in the microsomal transfer protein and Sar1b-GTPase genes, which affect the secretion of apoB containing lipoproteins. Dysbetalipoproteinemia stems from dysfunctional apoE and is characterized by the accumulation of remnants of chylomicrons and very low density lipoproteins. ApoE deficiency can cause a similar phenotype or rarely mutations in apoE can be associated with lipoprotein glomerulopathy. Low HDL can result from mutations in a number of genes regulating HDL production or catabolism; apoAI, lecithin: cholesterol acyltransferase and the ATP-binding cassette transporter ABCA1. Patients with cholesteryl ester transfer protein deficiency have markedly increased HDL cholesterol. Both common and rare genetic variants contribute to susceptibility to dyslipidemias. In contrast to rare familial syndromes, in most patients, dyslipidemias have a complex genetic etiology consisting of multiple genetic variants as established by genome wide association studies. Secondary factors, obesity, metabolic syndrome, diabetes, renal disease, estrogen and antipsychotics can increase the likelihood of clinical presentation of an individual with predisposed genetic susceptibility to hyperlipoproteinemia. The genetic profiles studied are far from complete and there is room for further characterization of genes influencing lipid levels. Genetic assessment can help identify patients at risk for developing dyslipidemias and for treatment decisions based on 'risk allele' profiles. This review will present the current information on the genetics and pathophysiology of disorders that cause dyslipidemias.
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PMID:Update on the molecular biology of dyslipidemias. 2654 29

Westernization of dietary habits leads to an increase in lipid intake and is thought to be responsible for an increase in patients with dyslipidemia. It is a well-known fact that the impaired cholesterol homeostasis is closely related to the development of various lifestyle-related diseases such as fatty liver, diabetes, and gallstone as well as dyslipidemia leading to atherosclerosis and cardiovascular diseases such as heart attack and stroke. Therefore, appropriate management of cholesterol levels in the body is considered important in prevention and treatments of these lifestyle-related diseases and in addition, molecular mechanisms controlling plasma (and/or hepatic) cholesterol levels have been intensively studied. Due to its hydrophobicity, cholesterol was long believed to pass through cell membranes by passive diffusion. However, recent studies have identified a number of plasma membrane transporters that are responsible for the cellular uptake or efflux of cholesterol and involved in developments of lifestyle-related diseases. In this review, we focus on Niemann-Pick C1 Like 1 (NPC1L1) and a heterodimer of ATP-binding cassette transporter G5 and G8 (ABCG5/G8), both of which are responsible for intestinal cholesterol absorption and biliary cholesterol secretion, and discuss the relationship between these cholesterol transporters and lifestyle-related diseases. In addition, we also discuss the related uncertainties that need to be explored in future studies.
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PMID:Associations between Lifestyle-Related Diseases and Transporters Involved in Intestinal Absorption and Biliary Excretion of Cholesterol. 2931 70