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)

Because hepatocyte growth factor (HGF) is a member of the endothelium-specific growth factors, we hypothesized that HGF may play a role in cardiovascular disease. Therefore we first examined the role of local HGF production in endothelial cell (EC) growth. Addition of anti-HGF antibody to EC resulted in a significant decrease in EC number. Moreover, coculture of vascular smooth muscle cells (VSMC) with EC resulted in an increase in EC number that was completely inhibited by anti-HGF antibody, suggesting that HGF secreted from EC and VSMC regulates EC growth in an autocrine-paracrine manner. Interestingly, transforming growth factor (TGF)-ss significantly decreased HGF secretion from EC, whereas interleukin 6 stimulated immunoreactive HGF secretion. In human VSMC, TGF-ss and angiotensin II suppressed local HGF production in a dose-dependent manner. Interestingly, anti-TGF-beta antibody resulted in significant but not complete inhibition of the decrease in local HGF production. To further study the regulation of local HGF production, we used a coculture system. Coculture of VSMC with EC resulted in a significant decrease in local HGF secretion. The decrease in local HGF production by coculture was significantly attenuated by anti-TGF-beta antibody, suggesting that inhibition of local HGF production in the coculture system was due to TGF-beta activation. Moreover, a further decrease in local HGF production in the coculture system by angiotensin II was also observed. Finally, we studied the role of angiotensin II in the regulation of the local HGF system in vivo by using a balloon injury rat model. Of importance, local HGF production was significantly decreased in balloon-injured arteries compared with intact vessels, accompanied by a reduction of HGF mRNA. An angiotensin-converting enzyme inhibitor (cilazapril) or an angiotensin II type 1 receptor antagonist (E-4177) significantly stimulated local vascular HGF production associated with the inhibition of neointimal formation after balloon injury compared with vehicle. In contrast, hydralazine did not alter local HGF production or neointimal formation despite decreasing blood pressure to a similar level as that in rats treated with cilazapril or E-4177. Overall, local HGF secretion from vascular cells was negatively regulated by TGF-beta and angiotensin II. The present study also demonstrated that blockade of angiotensin II significantly inhibited neointimal formation, accompanied by a significant increase in local vascular HGF production in vivo in the balloon injury model. Given the strong mitogenic activity of HGF on endothelial cells, increased local HGF production by blockade of angiotensin II may enhance reendothelialization after balloon injury. Downregulation of the local vascular HGF system by TGF-beta and vascular angiotensin may play an important role in the pathogenesis of cardiovascular diseases.
Hypertension 1998 Sep
PMID:Negative regulation of local hepatocyte growth factor expression by angiotensin II and transforming growth factor-beta in blood vessels: potential role of HGF in cardiovascular disease. 974 Jun 9

There is increasing evidence that systemic inflammation and insulin resistance constitute interrelated events that contribute to atherosclerosis. We studied the effect of the association between circulating interleukin 6 (IL-6) levels, one of the major mediators of inflammation, and C-reactive protein on insulin resistance and blood pressure in 228 healthy volunteers. The plasma IL-6 concentration was significantly and similarly associated with systolic (SBP) and diastolic (DBP) blood pressure, fasting insulin, and the fasting insulin resistance index (FIRI) in all subjects. When smokers were excluded from the analysis, plasma IL-6 levels correlated with percent fat mass (r = 0.19; P = 0.02), absolute fat mass (r = 0.17; P = 0.03), SBP, DBP, fasting insulin levels, and FIRI. The latter associations persisted after controlling for body mass index (r = 0.15 and r = 0.19; P = 0.02 and P: = 0.0004 for SBP and DBP, respectively; r = 0.24 and r = 0.19, P = 0.004 and P = 0.03, for fasting insulin and FIRI, respectively). Gender and smoking status significantly influenced the results. Although IL-6 levels were significantly associated with fasting insulin and FIRI in men, these significant correlations were not observed in women. Conversely, although IL-6 levels were significantly associated with SBP and DBP in women, these coefficients were not statistically significant in men. All of these associations were lost among smokers and remained significant in nonsmokers. As IL-6 is the major mediator of the acute phase response by hepatocytes and induces the synthesis of C-reactive protein (CRP), we also controlled for the latter. Serum CRP levels correlated significantly with IL-6 in all the subjects, but mainly in nonsmokers and men. Of note was that this significant relationship was lost among smokers. CRP was associated with fasting insulin (r = 0.28; P < 0.0001) and FIRI (r = 0.25; P < 0.0001), but not with SBP or DBP (P = NS), in all subjects. Unlike IL-6, the associations between CRP and these parameters were similar in men and women and in smokers and nonsmokers. For insulin and FIRI they were stronger in women and in nonsmokers. CPR significantly correlated with the WHR only in men (r = 0.22; P = 0.01). Using multiple linear regression in a stepwise manner to predict circulating IL-6 levels, smoking status (P = 0.0059) and FIRI (P = 0.03), but not fat mass or SBP, independently contributed to 11% of its variance in men. When CRP was introduced into the model, the latter (P < 0.0001) and smoking status (P = 0.02), but not FIRI, fat mass, or SBP, contributed to 33% of the variance in IL-6 levels. In women, only SBP (P = 0.04) contributed to 5% of its variance. When CRP was introduced into the model, again only SBP (P = 0.01) contributed to 10% of the variance in IL-6 levels. In 25 of these subjects, insulin sensitivity was determined using the frequently sampled iv glucose tolerance test with minimal model analysis, and circulating IL-6 levels were strongly associated with the insulin sensitivity index (r = -0.65; P < 0.0001). Again, this relationship was even stronger in men (r = -0.75; P < 0.001) and was not significant in women (r = -0.26; P = NS). In all of these subjects, only insulin sensitivity (P = 0.0037), not fat mass, contributed to 21% of the variance of IL-6 levels in a multiple linear regression analysis. In summary, circulating IL-6 levels, by inducing either hypertension in women or insulin resistance in men, constitute a significant proatherogenic cytokine. The mechanisms of these associations should be further investigated.
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PMID:Circulating interleukin 6 levels, blood pressure, and insulin sensitivity in apparently healthy men and women. 1123 1

Proinflammatory cytokines are capable of modulating cardiovascular function by a various mechanisms. The aim of the study was to evaluate the influence of the selected cytokines: tumor necrosis factor alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (L-6), endothelin 1 (ET-1) on the remodeling of the heart in patients with congestive heart failure (1-year follow-up). The study was made in 45 patients with congestive heart failure treated in the Department of Cardiology. Of these, 31 were men aged from 44 to 77 and 14 were women aged from 48 to 79. Ischaemic heart disease was diagnosed in 22 patients and ischaemic heart disease and hypertension in 10 patients, dilated cardiomyopathy was diagnosed in 6 patients and postinflammatory cardiomyopathy in 7 patients. Blood samples for determination of TNF-alpha, IL-1, IL-2, IL-6, ET-1, aldosterone, catecholamines, brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) levels were obtained prior to the treatment and in 3 and 6 and 12 month follow-up. At the same time were estimated: NYHA functional class, structure, systolic and diastolic left ventricle function of the heart using echocardiography and 24-hour ECG Holter monitoring (HR, supraventricular and ventricular arrhythmias). TNF-alpha, IL-1, IL-2, IL-6, ET-1, aldosterone, catecholamines, BNP and ANP plasma levels were determined with radioimmunological assay. In patients with progression of congestive heart failure (worsening of NYHA class and ejection fraction of left ventricle) the plasma concentrations of TNF-alpha and ET-1 significantly increased in following observations. In this group patients we determined a correlation between ejection fraction of the left ventricle and serum concentration of TNF-alpha and ET-1. In patients with improving of NYHA functional class and ejection fraction of left ventricle the plasma concentrations of cytokines were not altering. In all patients the plasma concentration of TNF-alpha correlated with ANP and BNP concentrations.
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PMID:[Cytokines and remodeling of the heart in patients with congestive heart failure]. 1287 63

Obese individuals are at increased risk from a range of metabolic diseases, including insulin resistance, dyslipidaemia and hypertension. Adipose tissue is an important endocrine organ, secreting a range of inflammatory mediators, including tumour necrosis factor alpha and interleukin 6. Circulating concentrations of these cytokines are increased in obesity and may contribute to the pathogenesis of metabolic diseases. The present review considers the evidence linking inflammation and obesity-related disease. The data show that an inflammatory phenotype, measured by serum sialic acid concentration, identifies individuals with insulin resistance, dyslipidaemia and hypertension. Serum sialic acid concentration increases progressively in obese individuals with none, one or multiple features of the metabolic syndrome, independent of BMI. Supplementation with long-chain n-3 polyunsaturated fatty acids has shown anti-inflammatory effects in studies of both healthy populations and in models of chronic inflammatory conditions. The effect on insulin sensitivity has been varied, with both positive and negative effects. This variability may relate to the metabolic characteristics of the study population; individuals with high background inflammation may derive greater benefits from n-3 polyunsaturated fatty acid supplements, suggesting a possible interaction between diet and phenotype. Future research is needed to fully evaluate the role of anti-inflammatory strategies in the dietary management of obesity.
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PMID:n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease. 1450 93

Normal metabolic balance is maintained by a complex homeostatic system involving multiple tissues and organs. Acquired or inherited defects associated to environmental factors in any part of this system can lead to metabolic disorders such as the syndrome X which is presently a frequent syndrome in industrialized countries. It is characterized by a cluster of risk factors of atherosclerosis including insulin resistance, hyperinsulinemia, impaired glucose tolerance or type 2 diabetes, hypertension, dyslipidemia, and coagulation abnormalities. Its pathophysiology is likely to involve insulin resistance at the level of both skeletal muscle and visceral adipose tissue and altered fluxes of metabolic substrates between these tissues that in turn impair liver metabolism. Therapeutic intervention favours at present diet and exercise prescriptions. In addition, if necessary, specific treatment of the metabolic disorders is required. In the treatment of insulin resistance, new promising drugs are likely to be used in the next future. In this regard, adipose tissue, once thought to function primarily as a passive depot for the storage of excess lipid, is now understood to play a much more active role in metabolic regulation, secreting a variety of metabolic hormones and actively functioning to prevent deleterious lipid accumulation in other tissues and to modulate the insulin resistance. Here, we review new advances in our understanding of mechanisms leading to insulin resistance and type 2 diabetes from the perspective of the role and interactions of recently identified adipocyte-specific chemical messengers, the adipocytokines, such as adiponectin, tumor necrosis factor-alpha, interleukin 6, and resistin.
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PMID:[Adipocytokins, obesity and development of type 2 diabetes]. 1459 11

Obstructive sleep apnea (OSA) is a common medical condition that occurs in approximately 5% to 15% of the population. The pathophysiology of OSA is characterized by repetitive occlusions of the posterior pharynx during sleep that obstruct the airway, followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. Obstructive sleep apnea is associated with daytime sleepiness and fatigue, likely due to fragmented sleep from recurrent arousals. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA and that OSA is a risk factor for the development of hypertension. Recent studies show that OSA may be implicated in stroke and transient ischemic attacks. Obstructive sleep apnea appears to be associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with preexisting pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified to be important in the development of atherosclerosis. Obstructive sleep apnea is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, and plasminogen activator inhibitor, and reduced fibrinolytic activity. Obstructive sleep apnea has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.
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PMID:Obstructive sleep apnea and cardiovascular disease. 1530 32

High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-alpha), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-alpha, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP >or=140 and/or diastolic BP >or=90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P=0.003), third (PR: 2.32; P=0.031), and fourth quartiles (PR: 2.30; P=0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-alpha levels were 1.41 (P=0.014) for the second; 1.59 (P=0.001) for the third; and 1.61 (P=0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-alpha and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.
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PMID:Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension. 1536 91

Hypertension is a serious health problem particularly for African-Americans. Previous studies have suggested that angiotensinogen (AGT) gene locus is involved in human essential hypertension. We have recently shown that an A/G polymorphism at -217 in the promoter of the AGT gene is associated with essential hypertension especially in African-Americans. We report here that A/G polymorphism at -217 affects the glucocorticoid-induced promoter activity of the human AGT gene. We show that recombinant glucocorticoid receptor (GR) binds strongly to the AGT gene promoter when nucleoside A is present at -217, and dexamethasone treatment increases the interleukin 6 induced promoter activity of reporter constructs containing nucleoside A at -217. Similarly cotransfection of GR and C/EBP beta or C/EBP delta increases the promoter activity of reporter construct containing nucleoside A at -217. Since AGT is an acute phase protein, we propose that increased expression of -217A allele of the AGT gene by glucocorticoids and C/EBP family of transcription factors may be involved in essential hypertension.
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PMID:A single-nucleotide polymorphism in human angiotensinogen gene is associated with essential hypertension and affects glucocorticoid induced promoter activity. 1563 May 92

Plasma phospholipid lipid transfer protein (PLTP) has several known key functions in lipoprotein metabolism. Recent studies suggest that it also may play a role in the inflammatory response. Inflammatory cell activity contributes to the development of atherosclerosis. To seek further evidence for the association of PLTP with inflammation, we studied the relationship between PLTP activity and five inflammatory markers [C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6), white blood cells (WBC), and fibrinogen] in 93 patients with low HDL and cardiovascular disease (CVD). Plasma PLTP activity had the strongest correlation with CRP (r=0.332, P<0.001) followed by SAA (r=0.239, P=0.021). PLTP, CRP, and SAA were significantly associated with body mass index (BMI), insulin or glucose, apolipoprotein (apo) B, and/or apo E level (r=0.264-0.393, P<0.01). PLTP, SAA, and IL-6 also were associated with the concentration of HDL particles without apo A-II [Lp(A-I)](r=0.373-0.472, P<0.005, n=56), but not particles with apo A-II. Smoking was associated with increased PLTP activity, CRP, and WBC, and hypertension with increased PLTP activity. In linear models, CRP remained significantly associated with PLTP after adjustment of CVD risk factors and insulin resistance. Also, much of the variability of plasma PLTP activity was explained by CRP, BMI, Lp(A-I), smoking, glucose, and blood pressure. These findings show for the first time that plasma PLTP activity is associated positively with CRP in CVD, a state of chronic inflammation.
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PMID:Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease. 1621 72

Obstructive sleep apnea (OSA) is a common medical condition that occurs in a considerable percentage of the population. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA is a risk factor for the development of hypertension. It is established that OSA may be implicated in stroke and transient ischemic attacks. OSA is associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with pre-existing pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified as important in the development of atherosclerosis. OSA is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.
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PMID:Inflammatory aspects of sleep apnea and their cardiovascular consequences. 1646 39


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