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)

The role of the adipose tissue in immunity has recently emerged, and there is now ample evidence that this role is elucidated by a number of cytokine-like hormones produced by adipocytes - called adipokines. The most relevant adipokines are leptin, adiponectin and visfatin, and all have marked effects on metabolic and immune function. The discovery of adipokines has led to the development of a novel concept that the pathogenesis of atherosclerosis can be associated with low-degree inflammation associated with slow (auto)immune attack of the endothelial wall of arteries. This model considers therefore adipokines as the bridge between atherosclerosis, inflammation and immunity. We review here the most recent advances on adipokine research, with a particular emphasis on the model that considers atherosclerotic lesions as effects of the (auto)immune-mediated damage of the endothelium that is sustained by low-degree chronic inflammation typical of obesity and metabolic syndrome.
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PMID:Leptin and adipocytokines: bridging the gap between immunity and atherosclerosis. 1822 Aug 5

Normal energy homeostasis requires a balance between fat storage and energy utilization that is guaranteed by regulation of one billion fat cells which arguably constitute the body's largest endocrine unit. Such physiology is required to maintain normal adiposity which if depleted from under- or malnutrition results in lipodystrophy that causes hormonal, reproductive, and developmental abnormalities. Conversely, excess adiposity provides inflammatory secretagogues, particularly from central visceral fat depots that enhance insulin resistance, excessive fatty acids with lipotoxicity and hypertension that escalate atherosclerosis including coronary artery disease. This review describes normal adiposity for maintenance of normal body mass and the roles of adipocyte hormones and adipokines for normal regulation of energy storage and its utilization. Therefore, in this context, the roles of leptin, insulin, adiponectin, and lesser known acylation-stimulating protein, visfatin, and apelin are outlined. Further, adipocyte inflammatory secretagogues are outlined that affect diabetes mellitus 2 with insulin resistance,fatty acid lipotoxicity, dyslipidemia, and hypertension that contribute to the metabolic syndrome. These effects are opposed by adipocyte hormones adiponectin, acylation-stimulating protein, visfatin, and apelin that help maintain normal energy utilization.
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PMID:The physiology of adiposity. 1839 31

Pre-B cell colony-enhancing factor (PBEF)/visfatin is produced by adipose tissue, skeletal muscle, bone marrow, the liver and lymphocytes. Although serum PBEF/visfatin is related to the pathogenesis of atherosclerosis, and its level is elevated in patients with chronic kidney disease, it remains unclear whether increased PBEF/visfatin is associated with atherosclerotic parameters in hemodialysis (HD) patients. In this study, we measured serum PBEF/visfatin in 68 chronic HD patients (age 66 +/- 14 years, time on HD 76 +/- 76 months, 41 males, 27 females) and examined the association of serum PBEF/visfatin with serum asymmetric dimethylarginine, arteriosclerotic parameters such as pulse wave velocity, ankle brachial pressure index and the percent of abdominal aortic wall calcification in a cross-sectional fashion. Serum PBEF/visfatin was significantly correlated with time on HD (r = 0.29, p = 0.02), but not with age, gender and diabetes. There was no association between PBEF/visfatin and body mass index, abdominal visceral and subcutaneous fat mass area, and total adiponectin. Serum PBEF/visfatin was significantly positively correlated with log-transformed highly sensitive C-reactive protein (r = 0.26, p < 0.05) but negatively with serum albumin (r = -0.33, p < 0.01). In contrast, there was no association between serum PBEF/visfatin and asymmetric dimethylarginine, aortic pulse wave velocity, brachial ankle pressure index and percent of abdominal aortic wall calcification. It follows from these findings that serum PBEF/visfatin may reflect the inflammatory status rather than atherosclerotic changes in chronic HD patients.
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PMID:Relationship between serum pre-B cell colony-enhancing factor/visfatin and atherosclerotic parameters in chronic hemodialysis patients. 1866 87

Recent researches have shown that adipocytokines secreted by adipose tissue play an important role in inflammation which is considered to be a crucial step in the pathogenesis of atherosclerosis. Leptin, one of the earlier adipocytokines, is known to play a major role in cardiovascular disease and recent observations suggest that leptin is an independent risk factor for coronary heart disease. Resistin, another recently discovered adipocytokine, has been related to risk factors of atherosclerosis, and in diabetic individuals serum resistin levels correlate well with inflammatory markers and are predictive for the development of cardiovascular disease. Adiponectin, another adipocytokine of interest in recent years, seems to be the most promising one studied to date. In contrast to leptin and resistin, adiponectin seems to be beneficial for health and it is a protective factor and decreased in obesity. However, many other factors derived from adipose tissue have also been discovered, such as interleukin-6, tumor necrosis factor alpha, monocyte chemoattractant protein 1, apelin, visfatin and probably others awaiting discovery in the near future. In this paper, we discussed the role of adipocytokines in the pathogenesis of atherosclerotic cardiovascular disease.
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PMID:A new frame in thromboembolic cardiovascular disease: Adipocytokine. 1837 21

The aim of the study were to answer the question 1.) Whether circulating pro-inflammatory markers of endothelial dysfunction and due to chronic low-grade inflammation of obesity, are altered in untreated lean, young relatively healthy polycystic ovary syndrome (PCOS) patients in comparison with healthy controls; 2.) Whether postprandial plasma concentration pattern of ghrelin and PYY can be predictable as risk factors for atherosclerosis and depend of obesity. Forty young women with PCOS were divided in two groups: 19 lean and 21 obese. The control group included 20 lean, healthy volunteers. Plasma total and active ghrelin, total PYY and PYY(3-36), serum adiponectin and insulin were measured using RIA technique, serum sCD40L, visfatin, sP-, sE-selectins, resistin by EIA. Composition of test meal was: 527 kcal total and consisted of 24.1% fat, 54.4% carbohydrate and 21.5% protein. Total and active ghrelin and total PYY were significantly lower in obese PCOS women, whereas active ghrelin was also significantly lower in lean PCOS women compared to controls. Postprandial plasma total ghrelin levels decrease were blunted in lean and obese compared to controls (12.8 % and 18.2% vs 28.2 %). Postprandial plasma active ghrelin decreased in lean and obese PCOS groups (49.9 % and 44.1 %) and controls (63.8 %). PCOS subjects exhibited smaller rises in postprandial levels of total PYY. Postprandial plasma PYY(3-36) levels increased in obese PCOS women (30.9 %) and controls (41%), whereas lean PCOS women exhibited blunted increase (11.5%). sCD40L levels increased, whereas adiponectin decreased in PCOS groups independently, whereas rise in visfatin, sE- and sP-selectin and the fall in adiponectin was associated with obesity. sP- and sE -selectins correlated positively with obesity. In summary, our study provides the first evidence that lean untreated young PCOS women contribute to the so called "pancreatic islet adaptation to insulin resistance" because of ghrelin and PYY profiles. We confirmed existing of low-grade chronic inflammation in early stage of visceral obesity in lean PCOS patients. The lost endogenous "islet adaptation to insulin resistance" may lead to endothelial dysfunction and promote acceleration of atherosclerosis.
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PMID:Postprandial response of ghrelin and PYY and indices of low-grade chronic inflammation in lean young women with polycystic ovary syndrome. 1881 36

Macrophages play key roles in obesity-associated pathophysiology, including inflammation, atherosclerosis, and cancer, and processes that affect the survival-death balance of macrophages may have an important impact on obesity-related diseases. Adipocytes and other cells secrete a protein called extracellular nicotinamide phosphoribosyltransferase (eNampt; also known as pre-B cell colony enhancing factor or visfatin), and plasma levels of eNampt increase in obesity. Herein we tested the hypothesis that eNampt could promote cell survival in macrophages subjected to endoplasmic reticulum (ER) stress, a process associated with obesity and obesity-associated diseases. We show that eNampt potently blocks macrophage apoptosis induced by a number of ER stressors. The mechanism involves a two-step sequential process: rapid induction of interleukin 6 (IL-6) secretion, followed by IL-6-mediated autocrine/paracrine activation of the prosurvival signal transducer STAT3. The ability of eNampt to trigger this IL-6/STAT3 cell survival pathway did not depend on the presence of the Nampt enzymatic substrate nicotinamide in the medium, could not be mimicked by the Nampt enzymatic product nicotinamide mononucleotide (NMN), was not blocked by the Nampt enzyme inhibitor FK866, and showed no correlation with enzyme activity in a series of site-directed mutant Nampt proteins. Thus, eNampt protects macrophages from ER stress-induced apoptosis by activating an IL-6/STAT3 signaling pathway via a nonenzymatic mechanism. These data suggest a novel action and mechanism of eNampt that could affect the balance of macrophage survival and death in the setting of obesity, which in turn could play important roles in obesity-associated diseases.
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PMID:Extracellular Nampt promotes macrophage survival via a nonenzymatic interleukin-6/STAT3 signaling mechanism. 1894 71

Obesity is associated with an array of health problems in adult and pediatric populations. Understanding the pathogenesis of obesity and its metabolic sequelae has advanced rapidly over the past decades. Adipose tissue represents an active endocrine organ that, in addition to regulating fat mass and nutrient homeostasis, releases a large number of bioactive mediators (adipokines) that signal to organs of metabolic importance including brain, liver, skeletal muscle, and the immune system--thereby modulating hemostasis, blood pressure, lipid and glucose metabolism, inflammation, and atherosclerosis. In the present review, we summarize current data on the effect of the adipose tissue-derived hormones adiponectin, chemerin, leptin, omentin, resistin, retinol binding protein 4, tumor necrosis factor-alpha and interleukin-6, vaspin, and visfatin on insulin resistance.
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PMID:Adipokines and insulin resistance. 1900 16

Monocyte chemotactic protein-1 and interleukin-6 are important inflammatory cytokines, which have close relationships with atherosclerosis. Visfatin is a novel adipokine involved in regulation of inflammatory cytokines, however, associations of visfatin with cytokines (MCP-1, IL-6) in human umbilical vein endothelial cells are unclear. The aim of this study was to determine whether visfatin has effects on the expression of MCP-1 and IL-6 in human umbilical vein endothelial cells. Enzyme-linked immunosorbent assay were used for measuring MCP-1 and IL-6 production in human umbilical vein endothelial cells. Real-time quantitative reverse-transcription polymerase chain reaction was used for determining MCP-1 and IL-6 mRNA expression. For the pathway determination following inhibitors were used: wortmannin [phosphatiylinositol 3-kinase (PI3K)], SB203580 [p38 mitogen-activated protein kinase (MAPK)], PD98059 [extracellular signal-regulated kinase (ERK) 1/2)], JNK inhibitor II [c-Jun NH 2-terminal kinase (JNK)]. We demonstrated that visfatin could obviously upregulate secretion of MCP-1and IL-6 in a dose- and time-dependent manner in human umbilical vein endothelial cells. Visfatin-induced effects were diminished by SB203580, wortmannin, and PD98059. In summary, these results suggest that visfatin-induced MCP-1 and IL-6 production involve p38 MAPK, PI3K, and ERK 1/2 pathways in human umbilical vein endothelial cells as determined by inhibition with specific inhibitors.
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PMID:Visfatin stimulates production of monocyte chemotactic protein-1 and interleukin-6 in human vein umbilical endothelial cells. 1900 99

Endothelial dysfunction is a characteristic of aging-related vascular disease and is worsened during diabetes. High glucose can impair endothelial cell (EC) function through cellular accumulation of reactive oxygen species, an insult that can also limit replicative lifespan. Nicotinamide phosphoribosyltransferase (Nampt), also known as PBEF and visfatin, is rate-limiting for NAD+ salvage from nicotinamide and confers resistance to oxidative stress via SIRT1. We therefore sought to determine if Nampt expression could resist the detrimental effects of high glucose and confer a survival advantage to human vascular EC in this pathologic environment. Human aortic EC were infected with retrovirus encoding eGFP or eGFP-Nampt, and FACS-selected to yield populations with similar, modest transgene expression. Using a chronic glucose exposure model we tracked EC populations to senescence, assessed cellular metabolism, and determined in vitro angiogenic function. Overexpression of Nampt increased proliferation and extended replicative lifespan, and did so preferentially during glucose overload. Nampt expression delayed markers of senescence and limited reactive oxygen species accumulation in high glucose through a modest increase in aerobic glycolysis. Furthermore, tube networks formed by Nampt-overexpressing EC were more extensive and glucose-resistant, in accordance with SIRT1-mediated repression of the anti-angiogenic transcription factor, FoxO1. We conclude that Nampt enables proliferating human EC to resist the oxidative stress of aging and of high glucose, and to productively use excess glucose to support replicative longevity and angiogenic activity. Enhancing endothelial Nampt activity may thus be beneficial in scenarios requiring EC-based vascular repair and regeneration during aging and hyperglycemia, such as atherosclerosis and diabetes-related vascular disease.
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PMID:Nicotinamide phosphoribosyltransferase imparts human endothelial cells with extended replicative lifespan and enhanced angiogenic capacity in a high glucose environment. 1930 75

Improving endothelial nitric oxide synthase (eNOS) bioactivity and endothelial function is important to limit native, vein graft, and transplant atherosclerosis. Visfatin, a NAD biosynthetic enzyme, regulates the activity of the cellular survival factor, Sirt1. We hypothesized that visfatin may improve eNOS expression, endothelial function, and postnatal angiogenesis. In human umbilical vein (HUVEC) and coronary artery endothelial cells, we evaluated the effects of recombinant human visfatin on eNOS protein and transcript expression and mRNA stability, in the presence and absence of visfatin RNA silencing. We also assessed visfatin-induced protein kinase B (Akt) activation and its association with src-tyrosine kinases, phosphorylation of Ser(1177) within eNOS in the presence and absence of phosphatidylinositol 3-kinase (PI 3-kinase) inhibition with LY-294002, and evaluated the contributory role of extracellular signal-regulated kinase 1/2. Finally, we determined the impact of visfatin on HUVEC migration, proliferation, inflammation-induced permeability, and in vivo angiogenesis. Visfatin (100 ng/ml) upregulated and stabilized eNOS mRNA and increased the production of nitric oxide and cGMP. Visfatin-treated HUVEC demonstrated greater proliferation, migration, and capillary-like tube formation but less tumor necrosis factor-alpha-induced permeability; these effects were decreased in visfatin gene-silenced cells. Visfatin increased total Akt and Ser(473)-phospho-Akt expression with concomitant rises in eNOS phosphorylation at Ser(1177); these effects were blocked by LY-2940002. Studies with PP2 showed that the nonreceptor tyrosine kinase, src, is an upstream stimulator of the PI 3-kinase-Akt pathway. Visfatin also activated mitogen-activated protein (MAP) kinase through PI 3-kinase, and mitogen/extracellular signal-regulated kinase inhibition attenuated visfatin-elicited Akt and eNOS phosphorylation. Visfatin-filled Matrigel implants showed an elevated number of infiltrating vessels, and visfatin treatment produced significant recovery of limb perfusion following hindlimb ischemia. These results indicate a novel effect of visfatin to stimulate eNOS expression and function in endothelial cells, via a common upstream, src-mediated signaling cascade, which leads to activation of Akt and MAP kinases. Visfatin represents a translational target to limit endothelial dysfunction, native, vein graft and transplant atherosclerosis, and improve postnatal angiogenesis.
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PMID:Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis. 1935 6


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