Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypoxia is an important topic both physiologically and clinically. Traditionally, physiology research has been focusing on the effect of acute and chronic sustained hypoxia and human adaptive response to high altitude. In the past 20 years, genetic studies by many have expanded our understanding of hypoxia to the molecular level. However, in contrast to our extensive knowledge about acute and chronic sustained hypoxia, we know relatively little about the effect of chronic intermittent hypoxia (CIH). In recent years, CIH has attracted more research attention because of the increasing prevalence of obesity and obstructive sleep apnea (OSA) in the western countries. Clinically, CIH is commonly seen in patients with sleep-disordered breathing including OSA, Cheyne-Stokes respiration and nocturnal hypoventilation. It was estimated that for OSA of at least mild severity prevalence estimates range from 3 to 28% in the general population. OSA is characterized by recurrent upper airway collapse during sleep leading to intermittent nocturnal hypoxia and sleep fragmentation. OSA is associated with significant mortality and morbidity including neurocognitive dysfunction, hypertension, many cardiovascular disorders and metabolic disorders such as diabetes and metabolic syndrome. The intermittent hypoxia in OSA closely mimics what is seen in the ischemia-reperfusion injury. Experimentally, there is no universally accepted definition for CIH. Laboratory protocols vary greatly in duration of hypoxia exposure, numbers of hypoxia episodes per day and the total number of days of exposure. Despite the lack of a uniform definition, recent data suggest that CIH may lead to multiple long-term pathophysiologic consequences similar to what we see in patients with OSA. Recent evidences also demonstrate that there are remarkable differences in the response of the physiologic systems to sustained hypoxia and intermittent hypoxia. This review is aimed to briefly discuss the clinical significance of sleep-disordered breathing and our current understanding of CIH.
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PMID:Obstructive sleep apnea and chronic intermittent hypoxia: a review. 1729 31

The metabolic syndrome (MS), a condition characterized by several risk factors for coronary artery disease, including obesity, is associated with endothelial dysfunction and oxidative stress. Because proper endothelial function is essential for signaling of certain growth factors (vascular endothelial growth factor, VEGF) we hypothesized that coronary collateral growth (CCG) is impaired in a model of the MS. To test this hypothesis, we stimulated coronary collateral growth in pre-diabetic Zucker obese fatty rats (OZR) and lean littermates (LZR) by using episodic, repetitive ischemia (RI: 40 s left anterior descending arterial occlusion, 24/d for 14 d). Myocardial blood flow (MBF, radioactive microspheres) was measured in the normal (NZ) and collateral-dependent (ischemic) zones (CZ); CCG was assessed as a ratio of CZ/NZ flow (unity represents complete restoration of CZ flow). In LZR, CZ/NZ ratio increased from 0.18 +/- 0.03 to 0.81 +/- 0.07 after RI (P < 0.05). In contrast, in OZR rats CZ/NZ did not increase after RI (0.15 +/- 0.04 vs 0.18 +/- 0.04). To rectify abrogated collateral growth in OZR, we employed VEGF gene therapy (VEGF-transduced, strained-matched, cultured vascular smooth muscle cells [cVSMCs], delivered intracoronary). VEGF therapy modestly but not significantly increased the CZ/NZ ratio after RI (0.16 +/- 0.05 vs 0.33 +/- 0.06). To facilitate VEGF signaling,we reduced oxidative stress by transducing cVSMCs with both ecSOD and VEGF. This increased the CZ/NZ flow ratio after RI to 0.52 +/- 0.04 (p < 0.05 vs. OZR [(0.19 +/- 0.04]) indicating partial restoration of collateral growth. Our results demonstrate that coronary collateral growth is impaired in a model of the metabolic syndrome and that growth factor gene therapy with VEGF is made far more effective when it is coupled to an intervention that reduces oxidative stress.
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PMID:Restoration of coronary collateral growth in the Zucker obese rat: impact of VEGF and ecSOD. 1732 99

Despite a dramatic decline in mortality over the past years, coronary heart disease is the leading cause of death and disability in the world. At the same time, with the great improvement of medical science, there is a growing population of postmyocardial infarction, postrevascularisation and heart failure survivors. Furthermore, there are rising rates of cigarette smoking, obesity, hypertension and the metabolic syndrome in the world. All the above contribute to the rising incidence rates of ischaemic heart disease (IHD) among women and men. This review highlights sex-specific issues in IHD presentation, evaluation and outcomes, with several new results published from the Women's Ischemia Syndrome Evaluation study. New evidence on traditional and novel risk markers as well as sex-specific differences in symptoms and diagnostic approaches have also been discussed.
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PMID:Recent development of ischaemic heart disease in sex difference. 1740 50

Small lipids such as eicosanoids exert diverse and complex functions. In addition to their role in regulating normal kidney function, these lipids also play important roles in the pathogenesis of kidney diseases. Increased glomerular cyclooxygenase (COX)1 or COX2 expression has been reported in patients with nephritis and in animal models of nephritis. COX inhibitors have shown beneficial effects on lupus nephritis and passive Heymann nephritis, but not anti-Thy1.1-induced nephritis. 5-Lipoxygenase-derived leukotrienes are involved in inflammatory glomerular injury. Lipoxygenase product 12-hydroxyeicosatetraenoic acid may mediate angiotensin II and transforming growth factor beta-induced mesangial cell abnormality in diabetic nephropathy. P450 arachidonic acid mono-oxygenase-derived 20-hydroxyeicosatetraenoic acid and epoxyeicosatrienoic acids are involved in several forms of kidney injury, including renal injury in metabolic syndrome. Ceramide also has been shown to be an important signaling molecule that is involved in the pathogenesis of acute kidney injury caused by ischemia/reperfusion and toxic insults. Those pathways should provide fruitful targets for intervention in the pharmacologic treatment of renal disease.
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PMID:Roles of lipid mediators in kidney injury. 1753 10

Arterial dysfunction is a hallmark of early atherosclerosis; however, its behavior in patients with metabolic syndrome (MS) is still unclear. We investigated the role of oxidative stress on ischemia-induced flow-mediated dilatation (FMD) in patients with MS. FMD and oxidative stress, as assessed by serum levels of 8-hydroxy-2-deoxy-2-deoxyguanosine (8-OHdG), were studied in 18 MS and 30 control subjects. Thereafter, in the 18 MS patients, FMD was assessed after iv infusion of 1 g vitamin C or placebo in a randomized, double-blind, crossover design; serial blood samples were taken in peripheral circulation before and after FMD to analyze 8-OHdG. Compared to controls, MS patients had higher 8-OHdG (p<0.001) and lower FMD (p<0.001); 8-OHdG and FMD were inversely correlated (R=-0.74; p<0.01). In MS patients, placebo administration did not change FMD, whereas vitamin C significantly enhanced it (p<0.001). After placebo, ischemia-induced FMD was associated with a significant increase in 8-OHdG (p<0.001), an effect that was counteracted by vitamin C. Vitamin C infusion was associated with an inverse correlation between the changes in FMD and oxidative stress (R=-0.67; p<0.01). The present study shows that arterial dilatation is impaired and that enhanced oxidative stress may play a key role in patients with MS.
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PMID:Oxidative stress-mediated arterial dysfunction in patients with metabolic syndrome: Effect of ascorbic acid. 1766 49

The ankle-brachial index (ABI) is a non-invasive, reliable measurement of lower-extremity ischemia. A low ABI is associated with increased risk of coronary heart disease, stroke and death. However, the relationship between ABI and all-cause mortality or cardiovascular disease (CVD) mortality in patients with metabolic syndrome (MetS) has not been well studied. Accordingly, we here investigated the association between ABI and all-cause and CVD mortality in an elderly Chinese population with MetS. A total of 2,274 MetS patients diagnosed under the criteria proposed by the International Diabetes Federation were divided into two groups based on repeated ABI measurement over a period of 13.6 months: ABI<or=0.9 (n=525) and ABI 0.91-1.4 (n=1,749). Each of the baseline characteristics of age, systolic blood pressure, diabetes mellitus morbidity, and smoking history were significantly different between the two groups (p<0.05 or p<0.01). All-cause mortality and CVD mortality decreased gradually as the ABI increased from 0.4 to 1.4. In Cox regression analysis, the relative ratio of all-cause mortality to CVD mortality also showed a tendency to decrease with increasing ABI. In elderly patients with MetS, ABI is one of the most important indexes for determining the possible prognosis and predicting all-cause and CVD mortality. People with relatively older age, higher systolic blood pressure, diabetes mellitus morbidity and smoking history may be at risk of lower ABI (<or=0.9) and higher all-cause and CVD mortality. Our results suggest the urgent need for repeated ABI measurement in clinical practice, both during individual visits and also over time, before diagnosing peripheral artery disease and making a therapeutic decision, especially in certain high-risk populations such as patients with MetS.
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PMID:The association between ankle-brachial index and cardiovascular or all-cause mortality in metabolic syndrome of elderly Chinese. 1778 29

Nonalcoholic fatty liver disease (NAFLD), the most common cause of steatosis, is associated with visceral obesity and insulin resistance. With more severe risk factors (obesity, type 2 diabetes [T2D], metabolic syndrome), steatosis may be complicated by hepatocellular injury and liver inflammation (steatohepatitis or NASH). NASH can lead to perisinusoidal fibrosis and cirrhosis. Fat-laden hepatocytes are swollen, and in steatohepatitis, further swelling occurs due to hydropic change (ballooning) of hepatocytes to cause sinusoidal distortion, as visualized by in vivo microscopy, reducing intrasinusoidal volume and microvascular blood flow. Involvement of other cell types (sinusoidal endothelial cells, Kupffer cells, stellate cells) and recruitment of inflammatory cells and platelets lead to dysregulation of microvascular blood flow. In animal models, the net effect of such changes is a marked reduction of sinusoidal space (approximately 50% of control), and a decrease in the number of normally perfused sinusoids. Such microvascular damage could accentuate further liver injury and disease progression in NASH. The fatty liver is also exquisitely sensitive to ischemia-reperfusion injury, at least partly due to the propensity of unsaturated fatty acids to undergo lipid peroxidation in the face of reactive oxygen species (ROS). This has important clinical consequences, particularly limiting the use of fatty donor livers for transplantation. In this review, we discuss available data about the effects of steatosis and steatohepatitis on the hepatic microvascular structure and sinusoidal blood flow, highlighting areas for future investigation.
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PMID:Hepatic microcirculation in fatty liver disease. 1848 15

Hearts of NaCl-induced hypertensive-glucose intolerant (HGI) rats develop reduced infarcts after ischemia-reperfusion injury (IRI) than their hypertensive (H) counterparts. Because high intake of saturated fat is a major risk factor for ischemic heart disease, we tested the hypothesis that chronic (18 weeks) consumption of a high saturated fat diet increases susceptibility to IRI, an effect more marked in the HGI rats than in the H rats. The fat-fed H (HFAT) rat displayed significantly higher body weight and plasma leptin content compared to the H, HGI, or fat-fed HGI (HGIFAT) rats which all showed similar values. In contrast, plasma triglyceride concentration was significantly higher in the HGIFAT rat than in the other three groups. Plasma insulin concentration was similar in the two H groups but higher than that of the two HGI groups. Compared to the H rat, the HGI rat was markedly glucose intolerant, with fat feeding causing comparable worsening of glucose intolerance in each group. The HGIFAT rats displayed a reduction in baseline myocardial contractility and relaxation and a higher end-diastolic pressure compared to the other three groups. Infarct size was significantly lower in the HGI rats than in the H rats. Although fat feeding did not affect infarct size of the H rat, it worsened that of the HGIFAT rat thereby abrogating the differential that existed between the H and HGI rats. In conclusion, excess fat feeding impairs myocardial function of HGI rats and increases their susceptibility to IRI. These findings are of relevance to the metabolic syndrome that manifests as a cluster of insulin resistance, dyslipidemia, and systemic hypertension.
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PMID:Myocardial ischemic-reperfusion injury in a rat model of metabolic syndrome. 1871 42

Obstructive sleep apnea (OSA), a highly prevalent breathing disorder in sleep, characterized by intermittent and recurrent pauses in respiration, has emerged as an independent risk factor for cardiovascular morbidity and mortality. Accumulated evidence implicates Leukocyte-endothelial cell activation and adhesion as critical components that induce inflammation and injury to the vasculature resulting in the development of cardiovascular complications. Similar cellular interactions were described in conditions of ischemia/reperfusion, and various components of the metabolic syndrome as hypercholesterolemia and hypertension. The hallmark of sleep apnea--the multiple cycles of hypoxia/reoxygenation--promote oxidative stress and inflammation. These facilitate increased interactions of blood cells with endothelial cells, resulting in endothelial cell injury and dysfunction. Such events can promote atherosclerosis and the development of cardiovascular morbidities in OSA. However, inter-individual differences in response to intermittent hypoxia and activation of anti-inflammatory cytokine profiles in T lymphocytes can serve as protective mechanisms.
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PMID:Biology of peripheral blood cells in obstructive sleep apnea--the tip of the iceberg. 1894 85

Diabetes, one of the major risk factors of metabolic syndrome culminates in the development of Ischemic Heart Disease (IHD). Refined diets that lack micronutrients, mainly trivalent chromium (Cr(3+)) have been identified as the contributor in the rising incidence of diabetes. We investigated the effect of niacin-bound chromium (NBC) during ischemia/reperfusion (IR) injury in streptozotocin induced diabetic rats. Rats were randomized into: Control (Con); Diabetic (Dia) and Diabetic rats fed with NBC (Dia+NBC). After 30 days of treatment, the isolated hearts were subjected to 30 min of global ischemia followed by 2 h of reperfusion. NBC treatment demonstrated significant increase in left ventricular functions and significant reduction in infarct size and cardiomyocyte apoptosis in Dia+NBC compared with Dia. Increased Glut-4 translocation to the lipid raft fractions was also observed in Dia+NBC compared to Dia. Reduced Cav-1 and increased Cav-3 expression along with phosphorylation of Akt, eNOS and AMPK might have resulted in increased Glut-4 translocation in Dia+NBC. Our results indicate that the cardioprotective effect of NBC is mediated by increased activation of AMPK, Akt and eNOS resulting in increased translocation of Glut-4 to the caveolar raft fractions thereby alleviating the effects of IR injury in the diabetic myocardium.
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PMID:Niacin bound chromium treatment induces myocardial Glut-4 translocation and caveolar interaction via Akt, AMPK and eNOS phosphorylation in streptozotocin induced diabetic rats after ischemia-reperfusion injury. 1902 47


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