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

Several studies support the association between postprandially elevated triglyceride levels and atherosclerosis. Histological and cell culture investigations revealed, that triglyceride rich postprandial lipoproteins are taken up by macrophages and smooth muscle cells and are detectable as part of foam cells in vascular lesions. Remnant particles, generated by lipolysis of postprandial lipoproteins in vitro and fatty acids increase the permeability of the endothelium and are cytotoxic for endothelial cells. Besides these morphological changes of cells, lipoproteins have been shown to exert effects on cellular functions like the expression of membrane proteins and the production or release of several bioactive substances regulating communication with blood cells and other cell systems of the vascular wall, blood pressure and hemostasis. This review concentrates on the influence of postprandial lipoproteins on factors involved in the interaction of endothelial cells with blood leukocytes and factors mediating blood pressure regulation. Increased expression of adhesion molecules has been detected immunehistochemically in atherosclerotic plaques in animals and humans. It was demonstrated that patients with elevated triglyceride levels have increased levels of soluble adhesion molecules. Furthermore, postprandial lipoproteins were shown to induce membrane expression of adhesion molecules. This effect seems to be at least in part mediated by the oxidative modification of the particles. Accordingly chylomicrons separated after ingestion of safflower oil, rich in polyunsaturated linoleic acid, induced higher adhesion molecule expression at higher oxidant concentration compared with chylomicrons separated after ingestion of olive oil, rich in monounsaturated oleic acid. Several authors described effects of fatty acids on the expression of adhesion molecules. On the one hand, they may exert stimulatory effects as such, on the other hand cytokine induced adhesion molecule expression may be enhanced by certain fatty acids and inhibited by others, implying an interference with signal transduction processes. Effects of lipoproteins on vasoactive substances seem to be implicated in endothelial dysfunction, too. The endothelium-derived relaxing factor nitric oxide (NO) has gained increasingly attention in the last two decades and is regarded as protective against hypertension and atherosclerosis. It was demonstrated that chylomicrons and their remnants inhibited endothelium-dependent relaxations in isolated aortas. Vasodilatatory responses and nitric oxide metabolism were shown to be affected by the amount and composition of dietary fat. Cell culture experiments revealed modulation of NO release by certain fatty acids. Plasma levels of endothelin-1, a strong vasoconstrictor, have been shown to be increased in patients with type 2 diabetes and metabolic syndrome, respectively. Postprandially elevated triglycerides increased endothelin-levels in addition to insulin in patients with metabolic syndrome. In summary, there is evidence that the association between postprandial triglycerides and the metabolic syndrome is driven by direct influences on endothelial functions because plasma triglyceride levels are associated with levels of humoral risk markers of endothelial origin, and postprandial lipoproteins stimulate the release and/or expression of endothelial mediators in vitro, which induce atherogenesis and hypertension.
 ...
PMID:Postprandial triglycerides and endothelial function. 1145 41

Cardiovascular disease is significantly increased in patients with metabolic syndrome and type 2 diabetes. Several factors such as chronic hyperglycemia, lipId abnormalities, endothelium dysfunction, inflammation, oxIdative stress, increased thrombosis and decreased fibrinolysis are likely to promote cardiovascular events in these patients. Because of positive effects on glucose homeostasis, lipId metabolism, proteins involved in all stages of atherogenesis, endothelium function, inflammation, thrombosis and fibrinolysis, PPARS alpha (fibrates) and PPARs gamma (glitazones) agonists are good candIdates to reduce cardiovascular disease, more precisely in subjects with metabolic syndrome or type 2 diabetes. PPARS alpha agonists (fibrates) are potent hypolipIdemic agents increasing plasma HDL-cholesterol and reducing free fatty acIds, triglycerIdes, LDL-cholesterol and the number of small dense LDL pArticles. Moreover, they reduce vascular inflammation and thrombosis, promote fibrinolysis and inhibit the production of the vasoconstrictor factor, endothelin-1, by the endothelium. They have been shown, in clinical trials, to reduce cardiovascular disease, more particularly in patients displaying lipId abnormalities typical of metabolic syndrome and type 2 diabetes (high triglycerIdes, low HDL-cholesterol). PPARS gamma agonists (glitazones) have not only beneficial effects on glucose homeostasis, by increasing insulin sensitivity and reducing blood glucose level but also on lipId metabolism by elevating plasma HDL-cholesterol, decreasing free fatty acIds and the number of small dense LDL pArticles, and for pioglitazone by reducing plasma triglycerIdes. Furthermore, they diminish vascular inflammation and vasoconstriction, inhibit monocyte chemotaxis, proliferation and migration of smooth muscle cells, in the vascular wall and decrease the production of adhesion molecules and metalloproteinases. PPARs gamma agonists (glitazones) have been shown to reduce the development of atherosclerotic lesions in rats. The potential clinical benefit of PPARs gamma agonists on the reduction of cardiovascular disease, in type 2 diabetic patients, will be specified by the ongoing intervention studies.
 ...
PMID:Clinical interest of PPARs ligands. 1502 92

Hypertension has been recognized as a multi-factorial trait resulting from the effect of a combination of environmental and genetic factors, including excess dietary salt or alcohol intake, stress, age, genetics and family history, obesity, physical inactivity, as well as high saturated fat diet. During the past few years, however, a large amount of information has been collected on the vascular inflammation, indicating that inflammation may involve in the initiation as well as development of hypertension and allowing us to reconsidering the pathogenic mechanisms of hypertension. Evidence from animal models as well as patients, have indicated that hypertension, an established major risk factor for coronary artery disease, has been suggested to exert pro-inflammatory actions through the increased expression of several mediators, including leukocyte adhesion molecules, chemokines, specific growth factors, heat shock proteins, endothelin-1, and angiotensin. The association between inflammation and hypertension recalls also a similar association between low-grade inflammation and other components of the metabolic syndrome, and endothelial dysfunction as well as increased serum levels of C-reactive protein in patients with hypertension. Is hypertension an inflammatory disease? This question has stimulated research on the role of vascular inflammation in hypertension. A better understanding of the inflammatory mechanism in hypertension may, therefore, contribute to novel therapeutic strategies to decrease the morbidity as well as mortality of hypertension, and alleviated hypertensive target organ damage.
 ...
PMID:Is hypertension an inflammatory disease? 1582 25

Increased oxidative stress in vascular cells plays a key role in the development of endothelial dysfunction and atherosclerosis. Uncoupling protein 2 (UCP2) is an important regulator of intracellular reactive oxygen species (ROS) production. This study was undertaken to test the hypothesis that, UCP2 functions as an inhibitor of the atherosclerotic process in endothelial cells. Adenovirus-mediated UCP2 (Ad-UCP2) overexpression led to a significant increase in endothelial nitric oxide synthase (eNOS) and decrease in endothelin-1 mRNA expression in human aortic endothelial cells (HAECs). Moreover, UCP2 inhibited the increase in ROS production and NF-kappaB activation, and apoptosis of HAECs induced by lysophophatidylcholine (LPC) and linoleic acid. LPC and linoleic acid caused mitochondrial calcium accumulation and transient mitochondrial membrane hyperpolarization, which was followed by depolarization. UCP2 overexpression prevented these processes. In isolated rat aorta, Ad-UCP2 infection markedly improved impaired vascular relaxation induced by LPC. The data collectively suggest that UCP2, functions as a physiologic regulator of ROS generation in endothelial cells. Thus, measures to increase UCP2 expression in vascular endothelial cells may aid in preventing the development and progression of atherosclerosis in patients with metabolic syndrome.
 ...
PMID:Effects of recombinant adenovirus-mediated uncoupling protein 2 overexpression on endothelial function and apoptosis. 1590 64

There is ample evidence from many epidemiological studies that lower urinary tract symptoms (LUTS) and sexual dysfunction are strongly linked, independently of age and comorbidities such as hypertension, diabetes, dyslipidaemia and coronary heart disease. However, a causal link between both conditions is not yet established. Four pathophysiological mechanisms currently support the relationship between LUTS and erectile dysfunction (ED): (i) The nitric oxide synthase (NOS)/NO theory; there is a reduction in NOS-containing nerves in the prostate and bladder/urethra in patients with bladder outlet obstruction (BOO), and that lack of NO or loss of protein kinase G causes ED; (ii) The autonomic hyperactivity and metabolic syndrome hypothesis: benign prostatic hyperplasia (BPH) may be part of the metabolic syndrome, which includes cardiovascular diseases (e.g. hypertension, ischaemic heart disease) and diabetes mellitus, known risk factors for ED. Hypertension, obesity, and hyperinsulinaemia have all been claimed to be associated with an increased sympathetic activity. Increased sympathetic activity is involved in LUTS/BPH and may have a role in ED/sexual dysfunction, with noradrenaline and alpha1-adrenoceptors representing a common link; (iii) the Rho-kinase activation/endothelin pathway; there can be increased Rho-kinase activity, and consequently calcium sensitivity of the contractile machinery, in prostate smooth muscle in BPH, the detrusor in BOO, corpora cavernosa in ED, and in the resistance vessels in hypertension. The actions of several factors beside noradrenaline (e.g. endothelin-1, angiotensin II), possibly involved in the increased smooth muscle activity found in both LUTS/BPH and sexual dysfunction, are dependent on Rho-kinase activity. Thus increased Rho-kinase activity might represent a common link between LUTS and sexual dysfunction; (iv) Pelvic atherosclerosis; animal models mimicking pelvic ischaemia and hypercholesterolaemia show similar smooth muscle alterations of the detrusor and corpora. Pelvic ischaemia may induce the biological modifications described above and may thus represent as well a common link between LUTS and sexual dysfunction. Studies treating one condition (e.g. ED) and measuring the impact on the other (e.g. LUTS) should further contribute to support this common link.
 ...
PMID:Lower urinary tract symptoms and sexual dysfunction: epidemiology and pathophysiology. 1650 50

Most of the basic components of the metabolic syndrome, namely type 2 diabetes mellitus, hypertension, obesity, or low high-density lipoprotein cholesterol levels, apart from being major risk factors for cardiovascular disease have been also associated with an increased risk of chronic kidney disease. However, several epidemiologic studies conducted over the past years suggest that the central component of the syndrome, insulin resistance, as well as compensatory hyperinsulinemia are independently associated with an increased prevalence of chronic kidney disease. In addition, background studies support the existence of several pathways linking insulin resistance and hyperinsulinemia with kidney damage. Insulin per se promotes the proliferation of renal cells and stimulates the production of other important growth factors such as insulin-like growth factor-1 and transforming growth factor beta. Insulin also upregulates the expression of angiotensin II type 1 receptor in mesangial cells, thus enhancing the deleterious effects of angiotensin II in the kidney, and stimulates production and renal action of endothelin-1. Moreover, insulin resistance and hyperinsulinemia are associated with decreased endothelial production of nitric oxide and increased oxidative stress which have been also implicated in the progression of diabetic nephropathy. This review analyzes the above and other potential mechanisms, through which insulin resistance and hyperinsulinemia can contribute to renal injury.
 ...
PMID:Insulin resistance, hyperinsulinemia, and renal injury: mechanisms and implications. 1673 48

Age-related reductions in basal limb blood flow and vascular conductance are associated with the metabolic syndrome, functional impairments, and osteoporosis. We tested the hypothesis that a strength training program would increase basal femoral blood flow in aging adults. Twenty-six sedentary but healthy middle-aged and older subjects were randomly assigned to either a whole body strength training intervention group (52 +/- 2 yr, 3 men, 10 women) who underwent three supervised resistance training sessions per week for 13 wk or a control group (53 +/- 2 yr, 4 men, 9 women) who participated in a supervised stretching program. At baseline, there were no significant differences in blood pressure, cardiac output, basal femoral blood flow (via Doppler ultrasound), vascular conductance, and vascular resistance between the two groups. The strength training group increased maximal strength in all the major muscle groups tested (P < 0.05). Whole body lean body mass increased (P < 0.05) with strength training, but leg fat-free mass did not. Basal femoral blood flow and vascular conductance increased by 55-60% after strength training (both P < 0.05). No such changes were observed in the control group. In both groups, there were no significant changes in brachial blood pressure, plasma endothelin-1 and angiotensin II concentrations, femoral artery wall thickness, cardiac output, and systemic vascular resistance. Our results indicate that short-term strength training increases basal femoral blood flow and vascular conductance in healthy middle-aged and older adults.
 ...
PMID:Resistance training increases basal limb blood flow and vascular conductance in aging humans. 1684 May 76

Endothelial dysfunction contributes to cardiovascular diseases that are also characterized by insulin resistance. Insulin resistance is a hallmark of metabolic disorders including Type 2 diabetes, obesity, and the metabolic syndrome that are also characterized by endothelial dysfunction. Metabolic actions of insulin to promote glucose disposal are augmented by vascular actions of insulin in endothelium to stimulate production of the vasodilator nitric oxide (NO). Indeed, NO-dependent increases in blood flow to skeletal muscle account for 25% to 40% of the increase in glucose uptake in response to insulin stimulation. PI 3-kinase-dependent insulin signaling pathways in endothelium related to production of NO share striking similarities with metabolic pathways in skeletal muscle that promote glucose uptake. Other distinct non-metabolic branches of insulin signaling pathways regulate secretion of the vasoconstrictor endothelin-1 (ET-1) in endothelium. Metabolic insulin resistance is characterized by pathway-specific impairment in PI 3-kinase-dependent signaling that in endothelium may cause imbalance between production of NO and secretion of ET-1 leading to decreased blood flow that worsens insulin resistance. Therapeutic interventions in both animal models and human studies demonstrate that improving endothelial function ameliorates insulin resistance while improving insulin sensitivity ameliorates endothelial dysfunction. Taken together, cellular, physiological, clinical, and epidemiological studies strongly support a reciprocal relationship between endothelial dysfunction and insulin resistance that helps to link cardiovascular and metabolic diseases. In this review, pathophysiological mechanisms that couple endothelial dysfunction with insulin resistance will be discussed with an emphasis on important therapeutic implications for the metabolic syndrome.
 ...
PMID:Reciprocal relationships between insulin resistance and endothelial dysfunction: insights from therapeutic interventions. 1685 13

1. Chronic feeding with a high-fat diet can cause metabolic syndrome in rodents similar to humans, but the role of saturated versus unsaturated fats in vascular tension remains unclear. 2. The present study shows that rats on a diet rich in either saturated or unsaturated fat had higher blood pressure compared with chow-fed rats (approximately 130 vs 100 mmHg, respectively), along with hyperlipidaemia and insulin resistance. Compared with responses of phenylephrine-preconstricted artery segments from chow-fed rats, vasorelaxation of isolated renal arteries from high-fat fed rats was reduced substantially (> 50%) in response to acetylcholine (0.01-10 micromol/L) and moderately to nitroprusside (>or=1 micromol/L) at low concentrations. Acetylcholine-induced vasorelaxation of arteries from high-fat fed rats was also more sensitive to inhibition by the nitric oxide (NO) synthase inhibitors NG-nitro-L-arginine and methylene blue. 3. In human umbilical vein endothelial cells, the production of NO and endothelin-1 was significantly inhibited by unsaturated fatty acids. In comparison, saturated fatty acids stimulated endothelin-1 production without altering NO production. 4. The data indicate that both saturated and unsaturated high-fat feeding may result in an increase in blood pressure owing to reduced endothelium-dependent vasorelaxation in the arterial system. The impaired endothelium-dependent vasorelaxation induced by saturated and unsaturated fatty acids may involve different mechanisms.
 ...
PMID:High-fat feeding reduces endothelium-dependent vasodilation in rats: differential mechanisms for saturated and unsaturated fatty acids? 1689 44

The mechanisms by which thiazolidinediones exert beneficial effects on the endothelium are still not clear. We examined the effects of rosiglitazone on the plasma markers of metabolic control (glucose, insulin, adiponectin, resistin, and lipid profiles), markers of inflammation (high-sensitivity C-reactive protein [CRP], interleukin-6, soluble CD40 ligand, intercellular adhesion molecule-1, and vascular cell adhesion molecule-1), and markers of vasoreactivity (asymmetric dimethylarginine [ADMA] and endothelin-1) and analyzed the relations between changes in endothelium-dependent flow-mediated dilation of the brachial artery and changes in these markers to elucidate their roles in mediating the vascular protective effects of rosiglitazone. Of 70 nondiabetic patients who met a modified National Cholesterol Education Program definition of the metabolic syndrome, 35 were randomized to receive rosiglitazone (4 mg/day) and 35 to receive placebo for 8 weeks. At study end, treatment with rosiglitazone had significantly reduced plasma insulin (-25%, p = 0.004) and resistin (-16%, p <0.001), increased adiponectin (164%, p <0.001), low-density lipoprotein cholesterol (16%, p = 0.005), and apolipoprotein-B (14%, p = 0.003), and decreased CRP (-30%, p = 0.005), soluble CD40 ligand (-20%, p = 0.014), ADMA (-16%, p <0.001), and endothelin-1 (-11%, p <0.001) concentrations and systolic and diastolic blood pressures. Rosiglitazone treatment significantly improved flow-mediated dilation (p <0.001) and nitroglycerin-induced vasodilation (p = 0.001) of the right brachial artery. On multivariate analysis, changes in ADMA, endothelin-1, and CRP were independent predictors of improved endothelial reactivity with rosiglitazone. In conclusion, we have, for the first time, demonstrated the independent associations between the improvement in flow-mediated dilation and reductions in ADMA, endothelin-1, and CRP after 8 weeks of treatment with rosiglitazone in nondiabetic patients with the metabolic syndrome. These findings suggest that decreases in ADMA, endothelin-1, and CRP may serve as possible mechanisms for the improvement in endothelial function conferred by rosiglitazone treatment.
 ...
PMID:Relation of improvement in endothelium-dependent flow-mediated vasodilation after rosiglitazone to changes in asymmetric dimethylarginine, endothelin-1, and C-reactive protein in nondiabetic patients with the metabolic syndrome. 1702 71


1 2 3 4 5 6 Next >>