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)

HYPERTENSION-ASSOCIATED ABNORMALITIES THAT PROMOTE CORONARY DISEASE: Although antihypertensive treatment has been effective in reducing premature cardiovascular mortality, the effect on various organ-specific morbid events has been unequal; the effect is much more impressive on stroke reduction than on reduction of coronary events. A student of pathophysiology would have anticipated such an outcome since blood pressure elevation is only one of multiple abnormalities in hypertension. Even in its mildest form hypertension is associated with the metabolic syndrome of dyslipidemia/insulin resistance which is conducive to early atherosclerosis. A large proportion of patients also have increased sympathetic and decreased parasympathetic tone, a constellation conducive to arrhythmias and, ultimately, to sudden death. An elevated hematocrit is also found in a substantial proportion of male patients and excessive platelet aggregability has also been described in hypertension. These hematologic abnormalities are conducive to coronary thrombosis. Angiotensin II and norepinephrine, two of the most potent trophic hormones, are frequently elevated in hypertension. The effect of these hormones on the cardiac and vascular structure further increases the predilection for negative outcomes. Left ventricular hypertrophy is a potent risk factor of coronary mortality, congestive heart failure and sudden death. Vascular hypertrophy reduces the coronary reserve and at the level of skeletal muscles contributes to the evolution of the metabolic syndrome. ORGAN-SPECIFIC HYPERTENSION TREATMENT: Because of these abnormalities we are entering a new era of treatment in hypertension. Whereas an effective fall in blood pressure remains the main goal of treatment, differential effects of various antihypertensive agents on organ-specific morbidity are being actively explored. If this research proves that certain drugs have a specific advantage in defined subgroups of patients, clinical practice will change. It is reasonable to expect that in the next century we will witness a further improvement in the impact of antihypertensive treatment on public health.
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PMID:Coronary disease in hypertension: a new mosaic. 921 91

Increased sympathetic tone is found in about 30% of patients with hypertension. This abnormality is closely associated with the metabolic syndrome of dyslipidaemia and hyperinsulinaemia. In this short review we discuss the mechanisms by which sympathetic over-activity could cause the metabolic syndrome. Sympathetic stimulation enhances cardiac and vascular hypertrophy. Left ventricular hypertrophy is a strong predictor of poor cardiovascular outcomes. Hypertrophy of resistance vessels accelerates hypertension, whereas hypertrophy of smaller coronary vessels limits coronary reserve and increases tendency for coronary spasms. Epidemiologically, high haematocrit is associated with hypertension and is recognized as an independent coronary risk factor. Sympathetic stimulation increases haematocrit through an increase of post-capillary vascular resistance. Sympathetic over-activity is also associated with platelet activation which may further add to the risk of coronary thrombosis in neurogenic hypertension. Tachycardia, which is due to increased sympathetic and deceased parasympathetic tone, is a hallmark of neurogenic hypertension. Fast heart rate is a strong predictor of coronary events and sudden death. The mechanisms by which tachycardia increases the cardiovascular risk are outlined.
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PMID:Effect of sympathetic overactivity on cardiovascular prognosis in hypertension. 965 30

Diabetes mellitus is increasing worldwide, resulting from the interaction of obesity, inflammation, and hyperglycemia. Activated immunity and cytokine production lead to insulin resistance and other components of the metabolic syndrome, establishing the link between diabetes and atherosclerosis. Hyperglycemia-induced endothelial dysfunction is mediated by increased oxidative stress, a promoter of adventitial inflammation and vasa vasorum neovascularization in experimental models of diabetic atherosclerosis. Recent studies have documented increased inflammation, neovascularization, and intraplaque hemorrhage in human diabetic atherosclerosis. This inflammatory microangiopathic process is independently associated with plaque rupture, leading to coronary thrombosis. Tissue factor, the most potent trigger of the coagulation cascade, is increased in diabetic patients with poor glycemic control. Circulating tissue factor microparticles are also associated with apoptosis of plaque macrophages, closing the link among inflammation, plaque rupture, and blood thrombogenicity. High-density lipoproteins, responsible for free cholesterol removal, are reduced in patients with insulin resistance and diabetes. High-density lipoprotein therapy leads to a significant decrease in plaque macrophages and increase in smooth-muscle cells. These beneficial effects may be responsible for coronary plaque stabilization in patients treated with recombinant Apolipoprotein A-I Milano/phospholipid complex. Finally, peroxisomal proliferator-activated receptors (PPARs) are now considered the nuclear transcriptional regulators of atherosclerosis. Three subfamilies, including PPAR-alpha, -delta, and -gamma, have been identified with crucial roles in lipid metabolism, plaque inflammation, expression of adhesion molecules and cytokines, and regulation of matrix metalloproteinases. Multiple experimental studies have documented plaque stabilization with PPAR-gamma agonists, a group of medications holding great promise in the treatment of diabetes atherosclerosis.
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PMID:New aspects in the pathogenesis of diabetic atherothrombosis. 1560 89

Metabolic syndrome is characterized by the clustering of a number of metabolic abnormalities in the presence of underlying insulin resistance with a strong association with diabetes and cardiovascular disease morbidity and mortality. The disorder is defined in different ways, but the pathophysiology is attributable to insulin resistance. An increased release of free fatty acids (FFAs) from adipocytes block insulin signal transduction pathway, induce endothelial dysfunction due to increased reactive oxygen species (ROS) generation and oxidative stress. Dyslipidemia, associated with high levels of triglycerides and low concentrations of high density lipoproteins (HDLs), contributes to a proinflammatory state. Inflammation, the key pathogenic component of atherosclerosis, promotes thrombosis, a process that underlies acute coronary event and stroke. Tissue factor, a potent trigger of the coagulation cascade, is increased in diabetes with poor glycemic control. Therapeutic lifestyle changes (weight loss and physical activity) along with pharmacological interventions are recommended to prevent the complications of metabolic syndrome. In addition to statins, metformin, blood pressure lowering medications, interventions to increase HDLs are other important approaches to decrease the risk of cardiovascular disease. Furthermore, the peroxisome proliferator activated receptor (PPAR)-alpha and gamma agonists are potent anti-inflammatory and anti-atherogenic agents that could both improve insulin sensitivity and the long-term cardiovascular risk. In this review we focus on the molecular and pathophysiological basis of metabolic syndrome, which augments diabetes (insulin resistance) and the contribution of neovascularization in the plaque progression in diabetes, leading to rupture and coronary thrombosis.
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PMID:Metabolic syndrome and diabetic atherothrombosis: implications in vascular complications. 1691 71

Atherothrombotic vascular disease is a complex disorder in which inflammation and coagulation play a pivotal role. Rupture of high-risk, vulnerable plaques with the subsequent tissue factor (TF) exposure is responsible for coronary thrombosis, the main cause of unstable angina, acute myocardial infarction, and sudden cardiac death. Tissue factor (TF), the key initiator of coagulation is an important modulator of inflammation. TF is widely expressed in atherosclerotic plaques and found in macrophages, smooth muscle cells, extracellular matrix and acellular lipid-rich core. TF expression can be induced by various stimulants such as C-reactive protein, oxLDL, hyperglycemia and adipocytokines. The blood-born TF encrypted on the circulating microparticles derived from vascular cells is a marker of vascular injury and a source of procoagulant activity. Another form of TF, called alternatively spliced has been recently identified in human and murine. It is soluble, circulates in plasma and initiates coagulation and thrombus propagation. Evidence indicates that elevated levels of blood-borne or circulating TF has been associated with metabolic syndrome, type 2 diabetes and cardiovascular risk factors and is a candidate biomarker for future cardiovascular events. Therapeutic strategies have been developed to specifically interfere with TF activity in the treatment of cardiovascular disease.
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PMID:Atherothrombosis: role of tissue factor; link between diabetes, obesity and inflammation. 1724 34

Diabetes and its associated chronic complications present a healthcare challenge on a global scale. Despite improvements in the management of chronic complications of the micro-/macro-vasculature, their growing prevalence and incidence highlights the scale of the problem. It is currently estimated that diabetes affects 425 million people globally and it is anticipated that this figure will rise by 2025 to 700 million people. The vascular complications of diabetes including diabetes-associated atherosclerosis and kidney disease present a particular challenge. Diabetes is the leading cause of end stage renal disease, reflecting fibrosis leading to organ failure. Moreover, diabetes associated states of inflammation, neo-vascularization, apoptosis and hypercoagulability contribute to also exacerbate atherosclerosis, from the metabolic syndrome to advanced disease, plaque rupture and coronary thrombosis. Current therapeutic interventions focus on regulating blood glucose, glomerular and peripheral hypertension and can at best slow the progression of diabetes complications. Recently advanced knowledge of the pathogenesis underlying diabetes and associated complications revealed common mechanisms, including the inflammatory response, insulin resistance and hyperglycemia. The major role that inflammation plays in many chronic diseases has led to the development of new strategies aiming to promote the restoration of homeostasis through the "resolution of inflammation." These strategies aim to mimic the spontaneous activities of the 'specialized pro-resolving mediators' (SPMs), including endogenous molecules and their synthetic mimetics. This review aims to discuss the effect of SPMs [with particular attention to lipoxins (LXs) and resolvins (Rvs)] on inflammatory responses in a series of experimental models, as well as evidence from human studies, in the context of cardio- and reno-vascular diabetic complications, with a brief mention to diabetic retinopathy (DR). These data collectively support the hypothesis that endogenously generated SPMs or synthetic mimetics of their activities may represent lead molecules in a new discipline, namely the 'resolution pharmacology,' offering hope for new therapeutic strategies to prevent and treat, specifically, diabetes-associated atherosclerosis, nephropathy and retinopathy.
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PMID:Specialized Pro-resolving Lipid Mediators: Modulation of Diabetes-Associated Cardio-, Reno-, and Retino-Vascular Complications. 3061 74