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

Resistin was initially identified as a protein, secreted by adipocytes, which inhibits insulin action and adipose differentiation. The three proteins homologous to resistin were termed resistin-like molecules (RELM) alpha, beta and gamma. Resistin and RELMalpha are abundantly expressed in adipose, but RELMbeta and RELMgamma are secreted mainly from the gut. Recently, resistin and RELMs were reported to be associated with inflammation. For example, RELMalpha, viewed as an inflammation-related protein, was originally identified in broncho-alveolar lavage fluid obtained from animals with experimentally induced pulmonary inflammation. RELMbeta is also related to bacterial colonization, but RELMbeta injection or hepatic overexpression of RELMbeta induced insulin resistance. RELMgamma isolated from rat nasal respiratory epithelium was found to be altered by cigarette smoke. Thus, resistin and RELMs could be useful for assessing the inflammatory condition in vivo. On the other hand, whether the serum resistin or RELM concentration is strongly related to insulin resistance remains unclear. However, taking recent studies showing a close relationship between inflammation and insulin resistance in diabetes into consideration, these proteins may have interactive roles linking inflammation and insulin resistance, both of which major involvement in the progression of atherosclerosis. If so, the serum resistin or RELM concentration may be a good marker of atherosclerotic risk. In addition, these proteins or unidentified receptors are potential therapeutic targets for the treatment of diabetes and prevention of atherosclerosis. These possibilities merit further study.
 ...
PMID:Physiological significance of resistin and resistin-like molecules in the inflammatory process and insulin resistance. 1822 Jun 47

Evidence has been provided that red wine possesses antiatherogenic activities in virtue of its content in polyphenols (flavonoids and non-flavonoids substances). Here, some red wines (Negroamaro, Primitivo and Lambrusco) were tested for their ability to trigger nitric oxide (NO) production from human healthy peripheral blood mononuclear cells (PBMC). Negroamaro was the strongest inducer of NO from PBMC and deprivation of polyphenols did not influence its NO generation capacity. This fact supports the involvement of polyphenols in the NO production even in the absence of alcohol, which also per se does not exert any significant activity. These results are also corroborated by the evidence that PBMC inducible-nitric oxide synthase expression occurred by the effect of samples containing polyphenols but this expression was very weak when polyphenols were removed from the whole Negroamaro. In synthesis, flavonoids and resveratrol, major constituents of red wine, once absorbed at intestinal level, enter circulation and trigger monocytes for NO production. To the best of our knowledge, this is the first demonstration of a direct effect of red wine on monocytes for NO release to occur. On the other hand, also the macrophage contingent from gut-associated lymphoid tissue can contribute to NO generation, besides the aliquot produced by endothelial cells, as previously demonstrated by various authors. Taken together, these results support the concept that moderate intake of red wine can prevent atherosclerosis via production of NO, a potent vasodilator of terminal vessels.
 ...
PMID:Red wine consumption and prevention of atherosclerosis: an in vitro model using human peripheral blood mononuclear cells. 1822 Aug 11

Color duplex ultrasound testing has evolved to be a clinically useful modality to diagnose chronic mesenteric ischemia caused by visceral artery origin atherosclerosis. Testing requires expertise in ultrasound imaging, visceral artery hemodynamics, and duplex scan interpretation. Patient can be accurately screened for severe stenosis or occlusion involving celiac, superior mesenteric, or inferior mesenteric arteries. Duplex testing can also evaluate functional patency following visceral bypass grafting procedures or endovascular stent-angioplasty. The focus of duplex surveillance after visceral artery intervention is to identify severe repair site stenosis, which can develop with symptoms of gut ischemia. Visceral duplex testing of a bypass graft or stent-angioplasty site that shows peak systolic velocities >300 cm/s with end-diastolic velocities >50 to 70 cm/s, or a decreased graft velocity peak systolic velocity <40 cm/s should be considered for interrogation using angiography to confirm or exclude severe (>70%) stenosis. Duplex testing after surgical or endovascular visceral interventions is a screening study, which compliments clinical follow-up by aiding the vascular surgeon in timely identification of visceral repairs that have developed a progressive, high-grade stenosis.
 ...
PMID:Visceral duplex scanning: evaluation before and after artery intervention for chronic mesenteric ischemia. 1828 48

Stimulation of Toll-like receptors, which serve to initiate inflammatory signaling in response to the detection of conserved microbial pathogen-associated molecular patterns (PAMPs), has been shown to play a central role in the development of atherosclerosis. In this review, the recent evidence supporting a role for both infection- and commensal-derived PAMPs in the pathogenesis of atherosclerosis will be discussed. Potential sources of PAMPs, their routes of delivery to the artery wall and the mechanisms by which PAMPs may affect vascular function independently of bacteremia or infection of the artery wall with viable organisms will be examined. Finally, the recent evidence that obesity and high-fat diets may each promote translocation of commensal-derived endotoxin from the gut into the circulation to induce inflammation, insulin resistance and atherosclerosis will be discussed.
 ...
PMID:The roles of pathogen-associated molecular patterns in atherosclerosis. 1830 95

Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily comprising four subtypes designated PPARalpha, PPARgamma1, PPARgamma2, and PPARdelta. These are transcription factors that regulate gene expression, thereby controlling energy metabolism. PPARgamma has widespread distribution in the adipose tissue, skeletal muscle, heart, liver, kidney, gut, macrophages, and vascular tissues. PPARgamma has a key role in adipogenesis, insulin sensitivity, and glucose and lipid metabolism, and also plays a major role in vascular biology, modulating atherosclerosis progression and vascular endothelial function. Thiazolidinediones (TZDs) are the ligands of PPARgamma, and growing evidence suggests that they might both directly and indirectly influence cardiovascular risk in type 2 diabetes patients by favorably altering several pro-atherogenic metabolic processes.
 ...
PMID:PPARgamma agonists and vascular risk factors: potential effects on cardiovascular disease. 1837 Jun 23

Exposure to lipids has a major effect on mammalian cells. Naturally, it has a profound impact on their metabolism, but it can also significantly alter their cellular and molecular phenotypes and responses. This latter is via specific signalling pathways leading to alterations in the expression of genes and gene networks. Multicellular organisms utilize a specialized group of proteins to detect and transduce lipid signals to the level of the expression of the genome. These proteins, termed nuclear hormone receptors, are lipid-activated transcription factors regulating gene expression upon binding of small fatty ligands. In this review, we discuss the role and contribution of peroxisome proliferator-activated receptor gamma (PPAR gamma) to macrophage and dendritic cell biology and also to gut epithelial cell function. We discuss how using different experimental systems and approaches the pathways activating the receptor and its target genes can be identified and complex biological processes unravelled. It appears that PPAR gamma is part of the macrophage's response to pathogenic lipoproteins and it coordinately regulates lipid uptake and efflux. Intriguingly, in another cell type of the immune system, dendritic cells, the receptor has overlapping, but distinct functions. In these cells, activation of PPAR gamma leads to altered immune phenotype characterized by increased phagocytic capacity, antigen processing and lipid antigen presenting capacity. This nuclear hormone receptor links lipid metabolism and immune cell function and these links provide unique insights into the regulatory logic of normal physiological responses and certain pathologies, such as atherosclerosis, chronic inflammatory diseases and autoimmunity.
 ...
PMID:Nuclear receptors, transcription factors linking lipid metabolism and immunity: the case of peroxisome proliferator-activated receptor gamma. 1883 94

Contemporary state of microecology of human gut was considered in light of ideas of I.I Mechnikov. It was shown that many ideas of our great countryman, which were expressed as far back as in the beginning of previous century, were confirmed in studies conducted in the last decades. It was calculated that total gene pool of microflora present in human organism which was named "microbiom", consists from 400,000 genes that is 12 times higher of human genome size. Such wide spectrum determines also huge functional activity of microorganisms, which participate in regulation of many physiological and immune reactions that provide protection of an organism from diseases, including infectious. Conception about fundamental role of facultative microflora in development of chronic inflammatory diseases of gastrointestinal tract was confirmed; the role of Gram-negative bacteria endotoxin in the development of atherosclerosis was established. Processes of interaction between products of intestinal microflora and pattern-recognizing Toll-like receptors (TLR), particularly TLR4, which recognizes endotoxins (lypopolysaccharides of Gram-negative microflora), were considered. It was shown that loss of TLR4 induced by mutation results in lowering of the risk of atherosclerosis.
 ...
PMID:[Ideas of I.I Mechnikov and contemporary microecology of human intestine]. 1900 80

Although most of us are more or less familiar with the term "cholesterol", the world of sterols is far more complicated and interesting. Apart from cholesterol, many non-cholesterol sterols can be found in human plasma and these sterols serve many important functions in human organism. They are either derived from endogenous biosynthesis of cholesterol or they come from dietary sources (phytosterols). The sole cholesterol molecule is used for keeping our cell membranes fit, for signalization purposes as well as a precursor for bile acids and steroid hormones. The compounds prior to cholesterol in its biosynthetic pathway were identified as vitamin D3 precursor, meiosis activating sterols and nowadays it seems that they could play a role in cholesterol homeostasis. The sterols from ingested vegetable sources, the phytosterols, are expelled from enterocytes and thus indirectly help our gut in coping with abundant cholesterol in the lumen. Higher plants synthesize many phytosterols, but in marine organisms, we can find other innumerous sterol molecules. The diversity of sterol molecules produced and resistance of their tetracyclic core to enzymatic activities implies crucial importance of sterols during the ontogenesis of multicellular organisms. First oxygen appeared on the Earth app. 2.7 billion years ago and since that time, every new life form took the advantage of oxygen needed also for build-up of sterol molecules. The last decades changed our view to the sterol molecules on almost at all levels of their appearance in human body. In the gut, the absorption of sterols was proven to be protein dependent and the quest for the transporter was successful. The general concepts of intracellular homeostasis of cholesterol have been described including the covalent interaction unbelievable so far - cholesterol and a protein. The clinical importance of non-cholesterol sterols rises with the effort to discover underlying facts about the causes of atherosclerosis. The compound in question, cholesterol, seems to be involved, but it sounds not to be crucial per se. The fact that the accumulation of phytosterols in sitosterolemia enhances the probability of early atherosclerosis onset further supports the hypothesis about some sterol (or steroid) compound being responsible on the molecular level for triggering the pathobiochemical cascade of events leading to atherosclerosis. Understanding the processes taking place in the enterocyte during the absorption of sterols resulted in synthesis of selective inhibitors at the level of sterol translocation into the enterocyte, sterol esterification and chylomicron packing, which are in different phases of clinical testing. The studies in the last part of the monograph represent the clinical potential of the analyses of non-cholesterol sterols. In well-defined groups, these analytes enables us to assess the changes in the homeostasis of cholesterol, which can be reflected in the concentration of total cholesterol. Furthermore, the high concentrations of some plasma sterols could point to the inborn errors of cholesterol biosynthesis (Smith-Laemli-Opitz syndrome), transport (sitosterolemia) or metabolization (cerebrotendinous xanthomatosis). Some issues concerning the research on the non-cholesterol sterols still remain unanswered - it is not known why some of the enzymes of the cholesterol biosynthesis (seladin-1, sterol D14 reductase) have other functions, qualitative aspects of sterol absorption are not satisfactorily explained and exact reason for expulsion of phytosterols from human body is not clear. Nevertheless, the authors hope that the presented facts can broaden the reader's perspective about the area, which is usually hidden beneath the cholesterol molecule.
 ...
PMID:Noncholesterol sterols. 1928 68

Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY...), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.
 ...
PMID:The role of the gut microbiota in energy metabolism and metabolic disease. 1944 72

Atherosclerosis is a leading cause of morbidity and mortality worldwide. Statins are established as first choice drugs for the management of hyperlipidaemia and cardiovascular risk. However, a residual cardiovascular risk, partially attributable to lipids, remains even after statin treatment. This risk appears to be associated with both high-density lipoprotein cholesterol and triglyceride lipid fractions. Several novel therapeutic approaches have been proposed to reduce lipid levels. Microsomal transfer protein (MTP) is involved in the assembly of very-low-density lipoprotein and chylomicron lipoprotein particles in the liver and the gut, respectively. In the preclinical setting, various agents that affect activity of MTP have shown that inhibition can result in profound reductions in blood triglycerides and cholesterol. Similarly, evidence of efficacy using the target has been confirmed in man with small molecule inhibitors and antisense oligonucleotides. Unfortunately, despite their efficacy in reducing lipids, the clinical utility of small molecule inhibitors has been restricted by their potential to induce hepatic steatosis. Continuing attempts to utilise this clinical target (to decrease cholesterol, triglycerides and weight) have involved the use of lower doses or non systemically absorbed MTP inhibitors.
 ...
PMID:Future challenges for microsomal transport protein inhibitors. 2070 Sep 2


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>