Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity which is defined as accumulation of excess body fat, is a major cause of atherosclerotic vascular disease in industrial countries. Recent advances in the biology of adipose tissue have revealed that adipose tissue is not simply an energy storage organ but it also secretes a variety of molecules which affect the metabolism of the whole body. Through a systematic search of active genes in adipose tissue, we found that adipose tissue, especially visceral fat expressed numerous genes for secretory proteins (about 30% of total genes analyzed). Among them, plasminogen activator-1 (PAI-1), which is a regulator of the fibrinolytic system, was overexpressed in the visceral fat in an animal model of obesity. Plasma levels of PAI-1 were closely correlated with visceral fat adiposity. Thus, PAI-1 secreted from visceral fat may play some role in thrombotic vascular disease in visceral obesity. Adiponectin, a novel adipose-specific gene product, which has a matrix-like structure, is abundantly present in the bloodstream. Dysregulated secretion of adiponectin may be related to vascular disease in obesity. Biologically active molecules secreted from adipose tissue (adipocytokines) may have important roles in the development of atherosclerotic disease in obesity.
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PMID:Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. 1022 88

Syndrome X is a clinical syndrome in which multiple risks cluster in an individual, and it is a common basis of vascular disease in the industrial countries. The molecular basis of Syndrome X, however, has not been elucidated. We have analyzed body fat distribution using CT scan and have shown that people who have accumulated intra-abdominal visceral fat frequently have multiple risks and vascular diseases. Thus, "visceral fat syndrome" is a clinical entity compatible with Syndrome X. To clarify the molecular mechanism of the disorders in visceral fat syndrome, we analyzed the expressed genes in adipose tissue by a large-scale random sequencing. Unexpectedly, visceral fat expressed a variety of the genes for secretory proteins including various bioactive substances; we designated them adipocytokines. One of them, plasminogen activator inhibitor-1, was overproduced in accumulated visceral fat and might contribute to the development of vascular disease. We have also cloned a novel adipose-specific gene named adiponectin. Adiponectin is a collagen-like plasma protein which has an inhibitory effect on proliferation of vascular smooth muscle cells; its plasma levels are paradoxically decreased in obesity. Adipocytokines may play important roles in the development of the disorders in Syndrome X.
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PMID:Molecular mechanism of metabolic syndrome X: contribution of adipocytokines adipocyte-derived bioactive substances. 1084 60

Visceral fat accumulation often accompanies various complications, such as insulin resistance, hypertension, dyslipidemia and atherosclerosis. Adipose tissue has been found to secrete various biologically active adipocytokines including free fatty acids. Accumulation of visceral fat increases the portal free fatty acids concentration to cause insulin resistance and dyslipidemia. Tumor necrosis alpha (TNF alpha) deteriorates insulin resistance in obesity. The levels of plasminogen activator inhibitor(PAI)-1 increase and plasma adiponectin concentration decreases in obesity leading to the development of vascular disease. The finding of genes specifically expressed in visceral fat and new adipocytokines should facilitate clarification of the mechanism for the development and complications of visceral fat accumulation.
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PMID:[Molecular mechanism in the development of the complications associated with obesity--the physiological and pathological role of adipocytokines]. 1126 96

Insulin resistance and its dreaded consequence, type 2 diabetes, are major causes of atherosclerosis. Adiponectin is an adipose-specific plasma protein that possesses anti-atherogenic properties, such as the suppression of adhesion molecule expression in vascular endothelial cells and cytokine production from macrophages. Plasma adiponectin concentrations are decreased in obese and type 2 diabetic subjects with insulin resistance. A regimen that normalizes or increases the plasma adiponectin might prevent atherosclerosis in patients with insulin resistance. In this study, we demonstrate the inducing effects of thiazolidinediones (TZDs), which are synthetic PPARgamma ligands, on the expression and secretion of adiponectin in humans and rodents in vivo and in vitro. The administration of TZDs significantly increased the plasma adiponectin concentrations in insulin resistant humans and rodents without affecting their body weight. Adiponectin mRNA expression was normalized or increased by TZDs in the adipose tissues of obese mice. In cultured 3T3-L1 adipocytes, TZD derivatives enhanced the mRNA expression and secretion of adiponectin in a dose- and time-dependent manner. Furthermore, these effects were mediated through the activation of the promoter by the TZDs. On the other hand, TNF-alpha, which is produced more in an insulin-resistant condition, dose-dependently reduced the expression of adiponectin in adipocytes by suppressing its promoter activity. TZDs restored this inhibitory effect by TNF-alpha. TZDs might prevent atherosclerotic vascular disease in insulin-resistant patients by inducing the production of adiponectin through direct effect on its promoter and antagonizing the effect of TNF-alpha on the adiponectin promoter.
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PMID:PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. 1152 76

Obesity is more linked to vascular disease, including atherosclerosis and restenotic change, after balloon angioplasty. The precise mechanism linking obesity and vascular disease is still unclear. Previously we have demonstrated that the plasma levels of adiponectin, an adipose-derived hormone, decreases in obese subjects, and that hypoadiponectinemia is associated to ischemic heart disease. In current the study, we investigated the in vivo role of adiponectin on the neointimal thickening after artery injury using adiponectin-deficient mice and adiponectin-producing adenovirus. Adiponectin-deficient mice showed severe neointimal thickening and increased proliferation of vascular smooth muscle cells in mechanically injured arteries. Adenovirus-mediated supplement of adiponectin attenuated neointimal proliferation. In cultured smooth muscle cells, adiponectin attenuated DNA synthesis induced by growth factors including platelet-derived growth factor, heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF), basic fibroblast growth factor, and EGF and cell proliferation and migration induced by HB-EGF. In cultured endothelial cells, adiponectin attenuated HB-EGF expression stimulated by tumor necrosis factor alpha. The current study suggests an adipo-vascular axis, a direct link between fat and artery. A therapeutic strategy to increase plasma adiponectin should be useful in preventing vascular restenosis after angioplasty.
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PMID:Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. 1213 20

Adiponectin is a novel polypeptide that is highly specific to adipose tissue. In contrast to other adipocytokines, adiponectin levels are decreased in obesity and associated comorbidities, such as type 2 diabetes. Decreased expression of adiponectin is correlated with insulin resistance. It has been suggested that several agents, such as tumor necrosis factor alpha, could mediate their effects on insulin metabolism through modulating adiponectin secretion from adipocytes. The mechanisms for the development of atherosclerotic vascular disease in obese individuals are largely unknown. Several findings support the interesting hypothesis that adiponectin could be a link between obesity and related atherosclerosis. First, adiponectin levels are lower in patients with coronary artery disease. Second, adiponectin modulates endothelial function and has an inhibitory effect on vascular smooth muscle cell proliferation. Moreover, adiponectin is accumulated more preferably to the injured vascular wall than intact vessels and has been shown to suppress macrophage-to-foam cell transformation. Adiponectin may also be involved in the modulation of inflammation. Thiazolidinediones, antiatherogenic and other effects have been explained by their direct enhancing effect on adiponectin. In conclusion, adiponectin has anti-inflammatory and antiatherogeneic effects as well as multiple beneficial effects on metabolism. Therefore it is not a surprise that adiponectin therapy has been tested in animal models of obesity, and it has been shown to ameliorate hyperglycemia and hyperinsulinemia without inducing weight gain or even inducing weight loss in some studies. Unlike agents that exert their effects centrally, adiponectin's effects seem to be peripherally mediated. The evidence of an association between adiponectin and the metabolic and cardiovascular complications of obesity is growing all the time.
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PMID:Adiponectin: a link between excess adiposity and associated comorbidities? 1243 46

Adiponectin, also called GBP-28, apM1, AdipoQ and Acrp30, is a novel adipose tIssue-specific protein that has structural homology to collagen VIII and X and complement factor C1q, and that circulates in human plasma at high levels. It is one of the physiologically active polypeptides secreted by adipose tIssue, whose multiple functions have started to be understood in the last few Years.A reduction in adiponectin expression is associated with insulin resistance in some animal models. Administration of adiponectin has been accompanied by a reduction in plasma glucose and an increase in insulin sensitivity. In addition, thiazolidinediones, drugs that enhance insulin sensitivity through stimulation of the peroxisome proliferator-activated receptor-gamma, increase plasma adiponectin and mRNA levels in mice. On the other hand, this adipocyte protein seems to play a protective role in experimental models of vascular injury. In humans, adiponectin levels are inversely related to the degree of adiposity and positively associated with insulin sensitivity both in healthy subjects and in diabetic patients. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type 2 diabetes mellitus, and also in patients with coronary artery disease. On the contrary, chronic renal failure, type 1 diabetes and anorexia nervosa are associated with increased plasma adiponectin levels. Concentrations of plasma adiponectin have been shown to correlate negatively with glucose, insulin, triglyceride levels and body mass index, and positively with high-density lipoprotein-cholesterol levels and insulin-stimulated glucose disposal. Weight loss and therapy with thiazolidinediones increased endogenous adiponectin production in humans. Adiponectin increases insulin sensitivity by increasing tIssue fat oxidation, resulting in reduced circulating fatty acid levels and reduced intracellular triglyceride contents in liver and muscle. This protein also suppresses the expression of adhesion molecules in vascular endothelial cells and cytokine production from macrophages, thus inhibiting the inflammatory processes that occur during the early phases of atherosclerosis. In view of these data, it is possible that hypoadiponectinemia may play a role in the development of atherosclerotic vascular disease. In summary, the ability of adiponectin to increase insulin sensitivity in conjunction with its anti-inflammatory and anti-atherogenic properties have made this novel adipocytokine a promising therapeutic tool for the future, with potential applications in states associated with low plasma adiponectin levels.
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PMID:The role of the novel adipocyte-derived hormone adiponectin in human disease. 1261 9

Insulin resistance and hyperinsulinemia are known atherosclerosis risk factors. The association between adiponectin plasma levels and obesity, insulinemia, and atherosclerosis has been shown. Thus, adiponectin may be a link between hyperinsulinemia and vascular disease. In vitro data demonstrated a reduction of adiponectin expression by insulin. However, it is still unclear whether insulin regulates adiponectinemia in vivo in humans. Five healthy male volunteers were studied. Circulating adiponectin levels were determined before and during hyperinsulinemic euglycemic clamp. Adiponectin was measured by radioimmunoassay. Hyperinsulinemia (85.0 +/- 33.2 at baseline vs. 482.8 +/- 64.4 pmol/l during steady state; p < 0.01) was achieved using a euglycemic hyperinsulinemic clamp, keeping blood glucose levels basically unchanged during the intervention (4.6 +/- 0.14 vs. 4.37 +/- 0.15 mmol/l, respectively; ns). We found a significant decrease of adiponectin plasma levels during the steady state of hyperinsulinemic euglycemic clamp (26.7 +/- 3.5 micro g/ml) compared to baseline levels (30.4 +/- 5 micro g/ml; p < 0.05). Hyperinsulinemia caused a significant decrease of adiponectin plasma levels under euglycemic conditions. Considering existing data about adiponectin dependent effects, hypoadiponectinemia might at least partly be a link between hyperinsulinemia and vascular disease in metabolic syndrome.
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PMID:Insulin decreases human adiponectin plasma levels. 1266 Aug 77

In this review article, the crucial roles of adipocytes in the development of so-called metabolic syndrome and vascular disease are reviewed, focusing on adipocyte-derived bioactive substances, adipocytokines. Recent progress in adipocyte biology shows that adipocytes are not merely energy-storing cells but that they secrete a variety of hormones cytokines, growth factors, and other bioactive substances. To search for novel adipocytokines by the large-scale random sequence analysis of expressed genes in adipocytes, we identified an adipose-specific collagen-like molecule, adiponectin. This novel adipocytokine has plural biofunctions, such as antidiabetic, antiatherosclerotic, and antiinflammatory functions. Adiponectin plasma levels decrease with the accumulation of visceral adipose tissue. In this review, we discuss the link of adiponectin to visceral adiposity, insulin resistance, and vascular diseases.
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PMID:Adiponectin and metabolic syndrome. 1455 Nov 51

To elucidate the biological characteristics of adipose tissue, we analyzed the gene expression profile of visceral and subcutaneous fat. Unexpectedly, adipose tissue, especially visceral fat, expressed a variety of genes for secretory proteins. About 30% of the genes expressed in visceral adipose tissue encoded secretory proteins and most were biologically active molecules, which we called adipocytokines. We found plasminogen activator inhibitor type 1 and heparin binding EGF-like growth factor. Production of these atherogenic adipocytokines was shown to increase with the accumulation of visceral fat, which may be one of the mechanisms of vascular disease in visceral obesity. We found a unique and novel collagen-like protein, adiponectin, encoded by the most abundantly expressed gene in adipose tissue, termed APM1 (adipose most abundant gene transcript-1). Plasma levels of adiponectin ranged from 0.3 to approximately 3 mg/dl but were decreased in patients with visceral obesity, type 2 diabetes and coronary artery disease (CAD). Screening for mutations in the adiponectin gene revealed that patients carrying a missense mutation showed markedly decreased plasma levels of adiponectin and had CAD. These data suggest that hypoadiponectinemia may be considered an important risk factor for CAD. Cell biology studies revealed that adiponectin has a potent inhibitory effect on the expression of adhesion molecules in endothelial cells and an inhibitory effect on the expression in macrophages. In order to confirm these antidiabetic and antiatherogenic functions of adiponectin, we developed adiponectin knockout mice. Adiponectin knockout mice showed severe insulin resistance and impaired glucose metabolism when fed a high-fat, high-sucrose diet. Knockout mice also developed intimal thickening in response to endothelial injury.
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PMID:Importance of adipocytokines in obesity-related diseases. 1467 98


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