Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is a growing body of clinical evidence that supports a strong association between elevated circulating trimethylamine N-oxide (TMAO) levels with increased risk of developing adverse cardiovascular outcomes such as atherosclerosis and thrombosis. TMAO is synthesized through a meta-organismal stepwise process that involves (i) the microbial production of TMA in the gut from dietary precursors and (ii) its subsequent oxidation to TMAO by flavin-containing monooxygenases in the liver. Choline, l-carnitine, betaine, and other TMA-containing compounds are the major dietary precursors of TMA. TMAO can also be absorbed directly from the gastrointestinal tract after the intake of TMAO-rich foods such as fish and shellfish. Thus, diet is an important factor as it provides the nutritional precursors to eventually produce TMAO. A number of studies have attempted to associate circulating TMAO levels with the consumption of diets rich in these foods. On the other hand, there is growing interest for the development of novel food ingredients that reduce either the TMAO-induced damage or the endogenous TMAO levels through the interference with microbiota and host metabolic processes involved in TMAO pathway. Such novel functional food ingredients would offer great opportunities to control circulating TMAO levels or its effects, and potentially contribute to decrease cardiovascular risk. In this review we summarize and discuss current data regarding the effects of TMA precursors-enriched foods or diets on circulating TMAO levels, and recent findings regarding the circulating TMAO-lowering effects of specific foods, food constituents and phytochemicals found in herbs, individually or in extracts, and their potential beneficial effect for cardiovascular health.
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PMID:Dietary bioactive ingredients to modulate the gut microbiota-derived metabolite TMAO. New opportunities for functional food development. 3268 2

Atherosclerosis is a chronic inflammatory disease of the arterial wall and is becoming the principal cause of death globally. The reverse cholesterol transport (RCT) mediated by Scavenger receptor class B type I (SR-BI) is a major protection mechanism against atherosclerosis. To investigate the metabolome changes and to find potential biomarkers involved in RCT, we applied nontargeted metabolomics and nontargeted lipidomics to SR-BI knockout mice fed a high fat and high cholesterol (HFHC) diet. SR-BI knockout mice and controls were told apart using multidimensional statistical analysis, and potential biomarkers were found and identified. The pathophysiological meaning of the biomarkers and the perturbed metabolic pathways were also addressed, which could provide new evidence for atherosclerosis studies. Statement of significance: We investigated the differences in plasma metabolome and lipidome in SR-BI knockout mice, for the first time, using liquid-liquid extraction method combined with nontargeted metabolomic and lipidomic approaches by high-performance liquid chromatography electrospray ionization tandem mass spectrometry. SR-BI knockout mice and controls were told apart using multidimensional statistical analysis. Metabolites with significant changes and pathways disturbed such as protein biosynthesis and vitamin B6 were addressed. Among the differentiated metabolites, gamma resorcylic acid was validated by authentic standard and appeared to be a predominant feature in SR-B1 knockout mice and may be used as a potential biomarker for cardiovascular disease. Decreased resorcylic acid may induce atherosclerosis with lower cholesterol efflux ability. After 8 weeks' high fat and high cholesterol diet, betaine level was decreased in SR-BI knockout mice, and valine and 2-Aminoadipic acid were increased in the knockout mice. These data indicated SR-BI may play multiple roles in atherosclerosis. This article is protected by copyright. All rights reserved.
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PMID:Plasma Metabolomic and Lipidomic Profiling of a Genetically Modified Mouse Model of Scavenger Receptor Class B Type I (SR-BI). 3296 44

The metabolism of methionine and cysteine in the body tissues determines the concentrations of several metabolites with various biologic activities, including homocysteine, hydrogen sulfide (H2S), taurine, and glutathione. Hyperhomocysteinemia, which is correlated with lower HDL cholesterol in blood in volunteers and animal models, has been associated with an increased risk for cardiovascular diseases. In humans, the relation between methionine intake and hyperhomocysteinemia is dependent on vitamin status (vitamins B-6 and B-12 and folic acid) and on the supply of other amino acids. However, lowering homocysteinemia by itself is not sufficient for decreasing the risk of cardiovascular disease progression. Other compounds related to methionine metabolism have recently been identified as being involved in the risk of atherosclerosis and steatohepatitis. Indeed, the metabolism of sulfur amino acids has an impact on phosphatidylcholine (PC) metabolism, and anomalies in PC synthesis due to global hypomethylation have been associated with disturbances of lipid metabolism. In addition, impairment of H2S synthesis from cysteine favors atherosclerosis and steatosis in animal models. The effects of taurine on lipid metabolism appear heterogeneous depending on the populations of volunteers studied. A decrease in the concentration of intracellular glutathione, a tripeptide involved in redox homeostasis, is implicated in the etiology of cardiovascular diseases and steatosis. Last, supplementation with betaine, a compound that allows remethylation of homocysteine to methionine, decreases basal and methionine-stimulated homocysteinemia; however, it adversely increases plasma total and LDL cholesterol. The study of these metabolites may help determine the range of optimal and safe intakes of methionine and cysteine in dietary proteins and supplements. The amino acid requirement for protein synthesis in different situations and for optimal production of intracellular compounds involved in the regulation of lipid metabolism also needs to be considered for dietary attenuation of atherosclerosis and steatosis risk.
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PMID:Sulfur-Containing Amino Acids and Lipid Metabolism. 3300 Jan 64


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