Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 and resistin are recently described secretory products of adipose tissue. Adiponectin is secreted by fat cells and circulates in the blood. Plasma adiponectin concentration is reduced in obese animals and humans and in patients with type 2 diabetes mellitus. Adiponectin stimulates fatty acids oxidation, decreases plasma triglycerides, and improves glucose metabolism by increasing insulin sensitivity. In addition, adiponectin inhibits the inflammatory process and possibly atherogenesis by suppressing the migration of monocytes/macrophages and their transformation into foam cells. Plasma adiponectin is lower in patients with ischemic heart disease than in body mass index-matched healthy individuals. Hypoadiponectinemia may contribute to insulin resistance and accelerated atherogenesis associated with obesity. Resistin/FIZZ3 is a member of the newly discovered cysteine-reach secretory protein family, referred to as 'resistin-like molecules' (RELM) or 'found in inflammatory zone' (FIZZ), together with FIZZ1/RELMalpha and FIZZ2/RELMbeta. Each of these has unique tissue distribution. Both resistin and FIZZ1/RELMalpha are expressed in adipose tissue. Initial studies in rodents suggested that resistin is upregulated in obesity and may be involved in the development of insulin resistance. Later studies failed to confirm this hypothesis and demonstrated reduced resistin expression in adipose tissue of obese animals. In human adipose tissue resistin is detectable at a very low level, and there is no relationship between resistin expression and obesity. Although the role of resistin in linking human obesity with type 2 diabetes is thus questionable, this protein is detected in peripheral blood monocytes,
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PMID:Adiponectin and resistin--new hormones of white adipose tissue. 1458 85

Adiponectin is an adipose-derived cytokine, and it is suggested that hypoadiponectinemia increases the prevalence of ischemic heart disease (IHD). The present study was undertaken to determine serum adiponectin levels in patients with arteriosclerosis obliterans (ASO) and IHD. Forty-nine patients with ASO and 49 age-, sex-, and body mass index-matched control subjects were examined. The diagnosis of ASO was derived from an ankle brachial index of less than 0.90 and stenotic or obstructive change in angiogram. Ischemic heart disease was diagnosed by ischemic or stenotic change in ECG, treadmill, or coronary angiogram. Serum adiponectin level was 8.6 +/- 0.9 microg/mL in the patients with ASO, a value significantly less than that of 12.4 +/- 1.0 microg/mL in the control subjects ( P < .01). Next, we subgrouped the subjects into 4 groups according to the presence of ASO and IHD. Serum adiponectin levels were 9.4 +/- 1.5 and 10.2 +/- 1.6 microg/mL in the subjects with ASO (n =23) and those with IHD (n = 13), respectively. It was further reduced to 7.9 +/- 1.2 microg/mL in the subjects having both ASO and IHD (n = 26), a value significantly less than that of 13.2 +/- 1.4 microg/mL in the control subjects (n = 36; P < .05). Serum high-density lipoprotein cholesterol was significantly less in the subjects with ASO than in the control subjects (42.1 +/- 1.7 vs 48.5 +/- 2.0 mg/dL; P < .05), but there were no differences in blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglyceride, and uric acid levels. The present results indicate that a reduction in serum adiponectin level is associated with the prevalence and magnitude of systemic atherosclerosis including IHD and ASO.
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PMID:Close association of hypoadiponectinemia with arteriosclerosis obliterans and ischemic heart disease. 1587 96

Obesity-related disorders are associated with the development of ischemic heart disease. Adiponectin is a circulating adipose-derived cytokine that is downregulated in obese individuals and after myocardial infarction. Here, we examine the role of adiponectin in myocardial remodeling in response to acute injury. Ischemia-reperfusion in adiponectin-deficient (APN-KO) mice resulted in increased myocardial infarct size, myocardial apoptosis and tumor necrosis factor (TNF)-alpha expression compared with wild-type mice. Administration of adiponectin diminished infarct size, apoptosis and TNF-alpha production in both APN-KO and wild-type mice. In cultured cardiac cells, adiponectin inhibited apoptosis and TNF-alpha production. Dominant negative AMP-activated protein kinase (AMPK) reversed the inhibitory effects of adiponectin on apoptosis but had no effect on the suppressive effect of adiponectin on TNF-alpha production. Adiponectin induced cyclooxygenase (COX)-2-dependent synthesis of prostaglandin E(2) in cardiac cells, and COX-2 inhibition reversed the inhibitory effects of adiponectin on TNF-alpha production and infarct size. These data suggest that adiponectin protects the heart from ischemia-reperfusion injury through both AMPK- and COX-2-dependent mechanisms.
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PMID:Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. 1621 Oct 35

AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge, being activated in situations of high-energy phosphate depletion. Upon activation, AMPK functions to restore cellular ATP by modifying diverse metabolic pathways. AMPK is activated robustly by skeletal muscle contraction and myocardial ischemia, and may be involved in the stimulation of glucose transport and fatty acid oxidation produced by these stimuli. In liver, activation of AMPK results in enhanced fatty acid oxidation and in decreased production of glucose, cholesterol, and triglycerides. Recent studies have shown that AMPK is the cellular mediator for many of the metabolic effects of drugs such as metformin and thiazolidinediones, as well as the insulin sensitizing adipocytokines leptin and adiponectin. These data, along with evidence from studies showing that chemical activation of AMPK in vivo with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) improves blood glucose concentrations and lipid profiles, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes and other metabolic disorders.
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PMID:AMP-activated protein kinase and type 2 diabetes. 1651 22

AMP-activated protein kinase (AMPK) is an enzyme that works as a fuel gauge which becomes activated in situations of energy consumption. AMPK functions to restore cellular ATP levels by modifying diverse metabolic and cellular pathways. In the skeletal muscle, AMPK is activated during exercise and is involved in contraction-stimulated glucose transport and fatty acid oxidation. In the heart, AMPK activity increases during ischaemia and functions to sustain ATP, cardiac function and myocardial viability. In the liver, AMPK inhibits the production of glucose, cholesterol and triglycerides and stimulates fatty acid oxidation. Recent studies have shown that AMPK is involved in the mechanism of action of metformin and thiazolidinediones, and the adipocytokines leptin and adiponectin. These data, along with evidence that pharmacological activation of AMPK in vivo improves blood glucose homeostasis, cholesterol concentrations and blood pressure in insulin-resistant rodents, make this enzyme an attractive pharmacological target for the treatment of type 2 diabetes, ischaemic heart disease and other metabolic diseases.
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PMID:AMP-activated protein kinase: Role in metabolism and therapeutic implications. 1702 83

The relation among adiponectin, renal function, and incident cardiovascular disease (CVD) in patients with different degrees of renal dysfunction was investigated. In total, 150 subjects were included in this study and followed prospectively for a mean of 32 months. At baseline, median adiponectin levels for chronic kidney disease (CKD) stages 1, 2, 3, 4 and 5, as estimated by creatinine clearance (> or =90, 60 to 90, 30 to 60, <30 ml/min), were 3.06, 4.04, 6.43, and 11.9 microg/ml, respectively (p for trend <0.01), and a significant association between adiponectin and CKD stages was also confirmed in multivariate regression analysis (F = 6.2, p <0.001). During follow-up, 31 subjects developed CVD, including myocardial infarction, angina pectoris, stroke, and transient ischemic attack. Gender-specific median values of adiponectin were used to separate the higher group from the lower group, and the Kaplan-Meier curve showed a significantly lower event-free survival rate in the lower adiponectin group (<4.39 microg/ml in men, <6.84 microg/ml in women, chi-square 4.88, p <0.03). The risk factor-adjusted Cox regression showed that an increase in adiponectin per 1 microg/ml was associated with a decrease in the risk of CVD to 0.86 (95% confidence interval 0.75 to 0.96, p = 0.004). In the subgroup with previous ischemic heart disease (IHD; n = 65), a significantly lower event-free survival rate of IHD was also observed in the lower adiponectin group (<4.45 microg/ml in men, <4.49 microg/ml in women, chi-square 3.96, p <0.05). The relative distribution of adiponectin isoforms was examined in patients with severe CKD, and the percentage of the high-molecular-weight form in patients with IHD during follow-up (n = 3) was significantly smaller than that in those without IHD (n = 4, p <0.02). In conclusion, renal function is a significant regulator of adiponectin when categorized by CKD stage, whereas hypoadiponectinemia is a predictor of CVD, including recurrent IHD.
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PMID:Adiponectin and renal function, and implication as a risk of cardiovascular disease. 1714 18

The present study was undertaken to determine serum adiponectin level in patients with cerebral infarction and to further analyze any difference in serum adiponectin levels among atherosclerotic disorders. One hundred fifty-two subjects with atherosclerotic disorders were enrolled, 110 males and 42 females, with the age of 67.0 +/- 9.9 years (mean +/- SD). They were divided into 62 patients with cerebral infarction, 48 patients with ischemic heart disease, and 42 patients with arteriosclerosis obliterans. Thirty-two subjects matched by age, gender, and body mass index served as controls. Serum adiponectin levels were 7.2 +/- 0.6 microg/mL (mean +/- SE) in the patients with cerebral infarction, 7.2 +/- 0.8 microg/mL in those with ischemic heart disease, and 6.9 +/- 0.9 microg/mL in those with arteriosclerosis obliterans. They were significantly less than the level of 12.6 +/- 1.9 microg/mL in the control group (P < 0.01). However, there was no difference in serum adiponectin level among three groups of atherosclerotic disorders. In the patients with acute cerebral infarction, serum adiponectin level was temporarily reduced from 7.3 +/- 0.9 to 6.2 +/- 0.8 microg/mL 14 days after the hospitalization (P < 0.01), followed by recovery to the basal value. The present findings indicate that serum adiponectin levels are equivalently reduced in patients with atherosclerotic disorders, and that serum adiponectin is changeable under acute phase of cerebral infarction.
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PMID:Hypoadiponectinemia in patients with cerebral infarction: comparison with other atherosclerotic disorders. 1749 31

The lipid-lowering and anti-atherosclerotic effects of atorvastatin (10 mg/day) were investigated by measuring changes in the levels of oxidized low-density lipoprotein (LDL), serum lipids (total cholesterol [TC], LDL-cholesterol [LDL-C] and triglycerides [TG]), and in the protein adiponectin. This was undertaken in 22 patients with ischaemic heart disease and serum LDL-C levels > 100 mg/dl. After 3 months of therapy, atorvastatin significantly decreased serum lipids, oxidized LDL was reduced from 457.0 +/- 148.6 to 286.9 +/- 88.5 nmol/l, and adiponectin increased from 9.7 +/- 7.4 to 13.9 +/- 9.98 microg/ml. No significant correlation was observed between adiponectin and LDL-C, TG and high-density lipoprotein cholesterol. Atorvastatin therapy was not associated with side-effects, such as myalgia and gastrointestinal disorders, and did not give abnormal laboratory test results. It is concluded that atorvastatin decreases serum lipid and oxidized LDL levels, and increases adiponectin levels in patients with ischaemic heart disease.
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PMID:Efficacy of atorvastatin therapy in ischaemic heart disease - effects on oxidized low-density lipoprotein and adiponectin. 1769 31

Metabolic syndrome is characterized by a cluster of metabolic disorders, such as reduced glucose tolerance, hyperinsulinemia, hypertension, visceral obesity and lipid disorders. The benefit of exercise in maintaining total metabolic control is well known and recent research indicates that AMP-activated protein kinase (AMPK) may play an important role in exercise-related effects. AMPK is considered as a master switch in regulating glucose and lipid metabolism. AMPK is an enzyme that works as a fuel gauge, being activated in conditions of high phosphate depletion. In the liver, activation of AMPK results in decreased production of plasma glucose, cholesterol, triglyceride and enhanced fatty acid oxidation. AMPK is also robustly activated by skeletal muscle contraction and myocardial ischemia, and is involved in the stimulation of glucose transport and fatty acid oxidation by these stimuli. In adipose tissue, activated AMPK inhibits deposition of fat, but enhances breakdown and burning of stored fat, resulting in reduction of body weight. The two leading diabetic drugs, namely metformin and rosiglitazone, and adipokines, such as adiponectin and leptin, show their metabolic effects partially through AMPK. These data suggest that AMPK may be a key player in the development of new treatments for obesity, Type 2 diabetes and the metabolic syndrome. In this review, the author provide insight into the role of AMPK as a probable target for treatment of metabolic syndrome.
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PMID:AMP activated protein kinase: a next generation target for total metabolic control. 1807 73


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