Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cells that make up blood vessel walls appear to participate actively in local immune and inflammatory responses, as well as in certain vascular diseases. We tested here whether smooth muscle cells (SMC) can produce the important inflammatory mediator IL6. Unstimulated SMC in vitro elaborated 5 X 10(3) pg recIL6/24h (i.e., biological activity equivalent to 5 X 10(3) pg recombinant IL6 (recIL6), as determined in B9-assay with a recIL6 standard). Several pathophysiologically relevant factors augmented IL6 release from SMC including 10 micrograms LPS/ml (10(4) pg recIL6), 10 ng tumor necrosis factor/ml (4 X 10(4) pg recIL6), and most notably 10 ng IL1/ml (greater than or equal to 3.2 X 10(5) pg recIL6). Production of IL6 activity corresponded to IL6 mRNA accumulation and de novo synthesis. SMC released newly synthesized IL6 rapidly, as little metabolically labeled material remained cell-associated. In supernatants of IL1-stimulated SMC, IL6 accounted for as much as 4% of the secreted proteins. In normal vessels SMC seldom divide, but SMC proliferation can occur in hypertension or during atherogenesis. We therefore tested the relationship between IL6 production and SMC proliferation in response to platelet-derived growth factor (PDGF) in vitro. Quiescent SMC released scant IL6 activity, whereas PDGF (1-100 ng/ml) produced concentration-dependent and coordinate enhancement of SMC proliferation and IL6 release (linear regression of growth vs. IL6 release yielded r greater than 0.9). IL6 itself neither stimulated nor inhibited SMC growth or IL6 production. Intact medial strips studied in short-term organoid culture produced large quantities of IL6, similar to the results obtained with cultured SMC. These findings illustrate a new function of vascular SMC by which these cells might participate in local immunoregulation and in the pathogenesis of various important vascular diseases as well as in inflammatory responses generally.
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PMID:Proliferating or interleukin 1-activated human vascular smooth muscle cells secrete copious interleukin 6. 231 24

Major genetic determinants of the metabolic syndrome - a clustering of abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high fasting glucose - remain elusive. We surveyed 207 single-nucleotide polymorphisms in 110 candidate genes among coronary artery disease patients, a population enriched for metabolic abnormalities. The number of abnormalities (0-5) was determined in the 214 male and 91 female patients, and the association with each polymorphism evaluated by means of ordinal regression analysis. Polymorphisms in eight genes, including LDLR, GBE1, IL1R1, TGFB1, IL6, COL5A2, SELE and LIPC, were associated with metabolic syndrome in the whole population ( P values ranged from 0.047 to 0.008). Variants in seven additional genes showed significant gene by gender interaction. Among these, separate analyses in men and women revealed a strong association with a silent polymorphism in the low-density lipoprotein receptor-related protein gene, LRPAP1, among females ( P=0.0003), but not males ( P=0.292). Other genes associated only in females included THBS1, ACAT2, ITGB3, F2 and SELP ( P values ranging from 0.032 to 0.002). Only one gene ( PRCP) was significantly associated in men alone ( P=0.039). Our results propose several new candidate genes for the metabolic syndrome and suggest that the genetic basis of this syndrome may be strongly modified by gender.
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PMID:Evidence for substantial effect modification by gender in a large-scale genetic association study of the metabolic syndrome among coronary heart disease patients. 1455 72

In 2005, new data on the prognostic value of blood pressure measurement in the home and by ambulatory recordings were published from the Italian (PAMELA) and Japanese (OHASAMA) registers. The ambulatory BP has a greater prognostic value than that measured in the physician's office in hypertensive patients whereas the difference in prognostic value is less in normotensive patients. The prevalence of masked hypertension is estimated at 15 to 26% with reference to the diastolic and systolic BP. The cardiovascular risk is significantly higher in patients with permanent or masked hypertension compared with normotensive subjects and "white coat" hypertensive patients. The ASCOT trial showed that in primary prevention of hypotensive patients with more than 3 associated cardiovascular risk factors, a strategy based on amlodipine secondarily associated with a diuretic, provided better control of the blood pressure than that of a betablocker secondarily associated with a diuretic: the therapeutic trial was negative with respect to the primary criterion including fatal coronary events and non-fatal myocardial infarction but the trial was stopped prematurely because of a significant reduction in cardiovascular and global mortality in the amlodipine-perindopril arm compared with the atenolol-thiazide arm. The metaregression of Verdecchia confirmed that the reduction of the BP remains the essential beneficial factor of antihypertensive therapy, but suggested that; in addition to the reduction of the blood pressure, ACE inhibitors provided better protection against coronary disease than calcium antagonists whereas the calcium antagonists were superior to ACE inhibitors for prevention of stroke. The endothelium is confirmed as a potential therapeutic target. Endothelial dysfunction has been demonstrated in resistance and conduction vessels. The study of antihypertensive therapy on endothelial vasodilation is a new pharmacological approach which may help differentiate the benefits of different classes. New data has documented the relations between inflammation, the vessel and hypertension, and different cytokines hs-CRP, ICAM1, IL6, TNF alpha and MCP-1 may be implicated. The new HAS 2005 recommendations for the management of adult hypertensive patients have been published recently; they are an updated reference for the optimisation of treatment in everyday clinical practice in France. The value of auto-measurement and ambulatory BP recording, the necessary estimation of global cardiovascular risk, the use of the 5 classes of antihypertensive drugs having shown a reduction in cardiovascular morbid-mortality, constitute the key points of these recommendations. Finally, data is now available concerning the incidence of hypertension in France in a working population (IPHAF study) and is estimated at 3% in men and 1.34% in women.
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PMID:[The best of hypertension 2005]. 1647 62

The aim of the present study was to assess the genetic risk for atherothrombotic cerebral infarction (ACI) in men and women separately as well as in individuals with or without conventional risk factors for atherosclerosis and thereby to contribute to the personalized prevention of ACI. The study population comprised 2705 unrelated Japanese individuals (1244 men, 1461 women), including 636 subjects (372 men, 264 women) with ACI. Subjects with ACI and controls either had or did not have conventional risk factors for atherosclerosis, including hypertension, hypercholesterolemia, and diabetes mellitus. The genotypes for 202 polymorphisms of 152 candidate genes were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. Multivariable logistic regression analysis and a stepwise forward selection procedure revealed that 11 different polymorphisms were significantly (P < 0.005) associated with ACI in women or men or in individuals with or without hyper-tension, hypercholesterolemia, or diabetes mellitus: the 584C-->T polymorphism of LIPG, 5665G-->T of EDN1, and G-->A of CCL11 in women; 677C-->T of MTHFR, 1323C-->T of ITGB2, 3932T-->C of APOE, and -231A-->G of EDNRA in men; -572 G -->C of IL6 in hypertensive individuals; -403G-->A of CCL5 and G-->A of COMT in individuals with hypercholesterolemia; and 3932T--> C of APOE and A-->G of TNFSF4 in diabetic individuals. Polymorphisms associated with ACI may thus differ between women and men as well as among individuals with different risk factors. Stratification of subjects on the basis of sex or conventional risk factors for atherosclerosis may therefore be important in order to achieve the personalized prevention of ACI with the use of genetic information.
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PMID:Genetic risk for atherothrombotic cerebral infarction in individuals stratified by sex or conventional risk factors for atherosclerosis. 1701 17

Impaired cytochrome P450 epoxygenase enzyme (Cyp2c) regulation contributes to renal damage in angiotensin salt-sensitive hypertension (ANG/HS). We hypothesized that interleukin-6 null mice (IL6-/-) would improve Cyp2c regulation and reduce renal damage in hypertensive mice fed a high salt diet. Systolic blood pressure increased to a greater extent in ANG/HS hypertension as compared to angiotensin (ANG) hypertension but blood pressure did not differ between WT and IL6-/- hypertensive groups. Albuminuria, a marker for renal injury, increased significantly in ANG/HS hypertension in WT mice (5,113 +/- 1,050 mug/day) and was attenuated in the ANG/HS IL6-/- group (1,306 +/- 385 mug/day). Renal Cyp2c protein expression significantly decreased with ANG/HS hypertension in WT mice as compared to high salt alone. However, the ability to upregulate Cyp2c expression in response to a high salt diet was restored in the ANG/HS IL6 deficient hypertensive mice. Renal expression of soluble epoxide hydrolase, which inactivates protective epoxygenase metabolites, was significantly reduced in ANG/HS IL6-/- hypertensive mice compared to the ANG/HS WT group. These data suggest that IL6, while having no effect on blood pressure, impairs regulation of epoxygenase producing Cyp2c, which could contribute to the development of renal injury in angiotensin salt-sensitive hypertension.
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PMID:IL6 suppression provides renal protection independent of blood pressure in a murine model of salt-sensitive hypertension. 1757 66

Essential hypertension is a common disease with fatal clinical complications. Epidemiological and family studies have confirmed the role of genetic predisposition in its development. Hypertensive patients have been shown to have an altered profile of pro- and anti-inflammatory cytokines. The aim of our investigation was to reveal the association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension and its clinical complications in a Tatar ethnic group from Bashkortostan, Russia. The study involved 362 hypertensive patients and 244 healthy subjects from this Tatar ethnic group (Bashkortostan, Russia). DNA was isolated from whole venous blood using phenol-chloroform extraction by the standard method. IL6 -572 G/C, IL12B 1159 C/A, and IL10 -627 C/A genotypes were typed using polymerase chain reaction followed by restriction enzyme digestion. We found that the IL10 -627 *C/*C genotype was associated with decreased risk of hypertension (OR = 0.64, P = 0.035). IL6 genotypes and allele distribution did not differ significantly between subjects with and without hypertension, but the IL6 -572 *G/*G genotype frequency was found to be significantly higher among those patients who had stroke, compared with normotensive control subjects (P = 0.036). Carriers of the IL12B 1159 *A/*A genotype had a lower risk of stroke (OR = 0.38, P = 0.028). Our study has shown the association between IL10 -627 C/A polymorphism and essential hypertension in the Tatar ethnic group from Bashkortostan, Russia. The IL10 -627*C/*C genotype was found to be protective against hypertension. We also demonstrated that hypertensive patients with the IL12B *A/*A and IL6 *G/*G genotypes had increased risk of stroke. Our results suggest a role for cytokines in cardiovascular disease development in the Tatar ethnic group, but further investigation is needed.
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PMID:Association of interleukin-6, interleukin-12, and interleukin-10 gene polymorphisms with essential hypertension in Tatars from Russia. 1816 9

Oxidative stress and inflammation are common manifestations and major mediators of cardiovascular and many other complications of end-stage renal disease (ESRD). Oxidative stress and inflammation are intimately interrelated as each can cause the other. The present study tested the hypothesis that antioxidant therapy may alleviate oxidative stress and improve inflammation in ESRD patients. We studied 37 hemodialysis patients, of whom 20 were treated daily with a combination of vitamin E, 800 lU; vitamin C, 250 mg; vitamin B6, 100 mg; vitamin B12, 250 microg; and folic acid, 10 mg; whereas 17 patients were given placebo for 8 weeks. Predialysis levels of f-2 isoprostane and protein carbonyl (markers of oxidative stress), C-reactive protein (CRP) and IL6 (markers/ mediators of inflammation) were measured prior to and at 4 and 8 weeks after the onset of therapy. Kt/V, predialysis and postdialysis blood pressure, blood hemoglobin, erythropoietin requirement, plasma ferritin and transferrin saturation, and nutritional indexes were similar among the 2 groups at baseline and remained virtually unchanged throughout the study period. Likewise, plasma f-2 isoprostane, protein carbonyl, CRP, and IL-6 levels remained unchanged and were unaffected by antioxidant administration. In conclusion, the addition of a potent antioxidant cocktail to conventional vitamin supplements had no effect on severity of ESRD-induced oxidative stress, inflammation, hypertension, anemia, or nutritional disorders in hemodialysis patients. Thus, high doses of vitamins beyond the routinely prescribed vitamin supplements do not appear to be indicated in this population.
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PMID:Antioxidant therapy does not ameliorate oxidative stress and inflammation in patients with end-stage renal disease. 1939 24

The clinical spectrum of preeclampsia (PE) ranges from mild hypertension to severe vasospasm associated with convulsions and multiple organ damage. The biological factors that determine the progression of PE to eclampsia (E) are unknown. Endothelial cell activation seems related to an impaired maternal immune response. The production of cytokines, IL-10 and TGF-beta1, is apparently suppressed, and altered IL-2/IL-10 and TNF-alpha/IL-10 ratios have been reported in preeclamptic cases. The relationship between PE and cytokine gene polymorphism has been studied, but there are few studies that include eclamptic patients. This study aimed at investigating whether polymorphisms in genes, TNF-alpha promoter (-308 G>A), IL6 promoter (-174 G>C), IFN-gamma intron 1 (+874 A>T), IL10 promoters (-1082 A>G), (-819 C>T) and (-592 C>A) and TGF-beta1 codon 10 (+869 T>C) and codon 25 (+915 G>C) are associated with E and/or PE. Genotyping was carried out in 266 Mulatto women from the northeastern region of Brazil who were referred to a single maternity hospital: 92 with PE, 73 with E and 101 normotensive controls. The chi(2) or Fisher's exact tests were used to compare genotype frequencies. Among the six single-nucleotide polymorphisms (SNPs) studied, we found no difference in genotype frequencies between the groups. There was a higher frequency of IFN-gamma (+874 A) in eclamptic patients in comparison with that in controls. (70.3 vs. 57.8%, respectively; P=0.02). There were no other significant differences in allelic frequencies between eclamptic, preeclamptic and control groups We found no independent association between any single SNP and PE or E risk in this population of Mulatto women from the northeastern region of Brazil.
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PMID:Cytokine gene polymorphisms in preeclampsia and eclampsia. 1940 22

Smoking, one of the avoidable causes of mortality, is considered a major risk factor for cardiovascular diseases, chronic obstructive pulmonary diseases, and bronchopulmonary cancer. Many studies suggest that nicotine induces vasoconstriction, not only in coronary arteries but also in peripheral vessels, hypertension, pro-atherogenic effects, due to increase of platelet activation and fatty acids concentration, alterations of endothelial-cell shapes, as well as endothelial-cell proliferation. The main affected vascular biochemical parameters are: endothelin-1, cholesterol, triglycerides, lipoproteins, C-reactive protein, nitric oxide, fibrinogen, and uric acid. Cigarette smoke induces inflammation in respiratory epithelium, through local irritation due to release of oxidants, aldehydes, acids, ammonium; impaired ciliar function, and retention of mucus and toxins, followed by infection; carcinogenesis due to oncogene-expression induced by oxidants, aromatic hydrocarbons, and nitrosamines. These effects are induced by alterations of endothelin-1, nitric oxide, IL1, IL6, TNF, and the CYP Enzyme System. Saliva is the first biological fluid encountered by the cigarette smoke. In vitro and in vivo salivary exposure to cigarette smoke has been shown to determine changes of concentrations of lactate dehydrogenase, amylase, and uric acid, in saliva--important factors of the antioxidant salivary system. Such changes may promote occurrence of upper digestive cancers.
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PMID:[The role of smoking in changing essential parameters in body homeostasis]. 1963 60

The aim was to study the stimuli responsible for triggering and sustaining the plasma concentration of the inflammatory marker interleukin-6 (IL-6) in patients with a first myocardial infarction before the age of 60 and healthy control subjects matched for age and sex. The plasma IL-6 concentration, antibodies against Chlamydia pneumoniae, cytomegalovirus, Epstein-Barr virus, Helicobacter pylori, herpes simplex type 1 and 2, and genotype for the IL6-174 G>C single-nucleotide polymorphism were determined 3 months after the acute event. The results showed that patients had higher IL-6 levels than control subjects, whereas there were no differences regarding individual or total number (pathogen burden) of positive antibody tests against the different pathogens or IL6 genotype distribution. The plasma IL-6 concentration was associated with the number of positive antibody tests in patients and control subjects, whereas patients irrespective of IL6 genotype had increased IL-6. Multivariate analysis, including traditional coronary heart disease risk factors, antibodies against pathogens, and IL6 genotype, explained 17% of the variation of the plasma IL-6 concentration. Neither pathogen burden nor IL6 genotype did contribute to the variation of plasma IL-6 levels, whereas smoking, body-mass index, hypertension, case-control status, and age were determinants of the plasma IL-6 concentration.
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PMID:Genetic and environmental influences on the plasma interleukin-6 concentration in patients with a recent myocardial infarction: a case-control study. 2108 78


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