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

The plasmid pMK16 containing-SV40 replicated origin defective gene was efficiently introduced into early-passage human umbilical vein endothelial cells (HUVEC) using positively charged liposomes. The resulting cell line acquired an almost infinite lifespan, was morphologically unchanged, expressed SV40-antigen, and coexpressed von Willebrand factor (vWF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), angiotensin conversion enzyme (ACE), and endothelin converting enzyme (ECE). In addition, these are the first immortalized human endothelial cells, to our knowledge, that biosynthesized and secreted interleukins (IL-1 beta and IL-6) in both a constitutive and regulated fashion and endothelin-1 (ET-1), the most potent vasoactive peptide, which has been suggested to be implicated in the pathogenesis of hypertension. Interestingly enough, both of the immortalized cells and the early-passage HUVEC from which the immortalized cells were obtained biosynthesized and secreted the same levels of ET-1 suggesting full maintenance of its biosynthetic pathway including the presence of active ECE, which cleaves big endothelin-1 (big-ET-1) to ET-1 and regulation factors. Moreover, the immortalized cells retained the ability to express the functional specific amino acid Na(+)-independent system Y+ transporter, which mediates L-arginine transport into endothelial cells from which endothelium-derived relaxing factor (EDRF, nitric oxide) is formed via the action of nitric oxide-synthase. Obtaining these immortalized human endothelial cells without alteration of the differentiated characteristics constitutes a useful model: (a) to study ET-1 secretion, gene regulation, and human ECE, which may be an important therapeutic target in disease conditions in which ET-1 is to be implicated; (b) to study L-arginine transport, which is a key step in the formation of EDRF; (c) to study IL-1 beta and IL-6 secretions, and gene regulations; (d) to substitute large quantities of HUVEC; and, finally, (e) to reproduce, starting with different primary endothelial cells both from human and animal origin.
 ...
PMID:Establishment of permanent human endothelial cells achieved by transfection with SV40 large T antigen that retain typical phenotypical and functional characteristics. 883 14

Obesity is commonly associated with insulin resistance. The etiology of insulin resistance syndrome such as syndrome X or deadly quartet is not clear. We have proposed visceral fat syndrome, in which fat accumulation is predominant in the intra-abdominal cavity, frequently accompanied by disorders of glucose and lipid metabolism, and also hypertension. Excess free fatty acid of the portal circulation may cause the enhancement of lipid synthesis and gluconeogenesis as well as insulin resistance, resulting in hyperlipidemia, glucose intolerance and hypertension and finally atherosclerosis. Enhanced production of PAI-1 by increased visceral fat may be partly responsible for the development of cardiovascular disease in patient with visceral fat assmulation.
 ...
PMID:[Obesity and insulin resistance syndrome]. 891 27

We examined the association between psychosocial stress-related variables and insulin resistance syndrome (IRS) risk-factor clustering. In 90 middle-aged male volunteers, psychosocial stress-related variables, defined as feelings of excessive tiredness and as personality and behavioral factors reflecting a stress-inducing life-style (type A behavior, hostility, and anger), were significantly correlated with the hyperinsulinemia, hyperglycemia, dyslipidemia, hypertension, increased abdominal obesity, and increased plasminogen activator inhibitor-1 (PAI-1) antigen comprising the IRS. The correlations remained significant after adjusting for body mass index (BMI), age, educational level, smoking status, alcohol consumption, and physical activity. However, the different stress-related factors reflected different risk-factor clustering profiles. Type A behavior was associated with normotension and a normal metabolic profile (canonical r = .50, chi2(36) = 59.1, P = .008). Hostility was related to elevated systolic blood pressure (SBP) and elevated triglycerides (TGs) (canonical r = .38, chi2(14) = 23.2, P = .052), whereas feelings of excessive tiredness were related to abdominal obesity, augmented glycemic responses to glucose ingestion, dyslipidemia, and increased PAI-1 antigen (canonical r = .39, chi2(24) = 36.8, P = .046). Although hostility and feelings of excessive tiredness have partly overlapping but clearly different clinical and metabolic correlates, their combination represents a full-blown IRS. Thus, even though insulin resistance is presumably to some extent genetically determined, these results suggest that considering psychosocial stress may be beneficial in understanding IRS risk-factor clustering.
 ...
PMID:Psychosocial stress and the insulin resistance syndrome. 896 88

The expression of transforming growth factor-beta 1 (TGF-beta 1) for hypertensive renal injury was investigated in Dahl salt-sensitive (Dahl-S) rats fed a high-salt (HS; 8% NaCl) diet or a low-salt (LS; 0.3% NaCl) diet for 4 wk. The HS rats developed severe hypertension and renal damage, including glomerulosclerosis and arteriosclerosis. TGF-beta biosynthesis by isolated glomeruli, the TGF-beta localization, and the gene expression of TGF-beta 1, latent TGF-beta binding protein (LTBP), and TGF-beta receptors (Types I, II, and III) were compared between the HS rats and LS rats. A TGF-beta bioassay revealed that the isolated glomeruli from the HS rats secreted a larger amount of latent TGF-beta than those from the LS rats. Northern blotting analysis demonstrated that the HS diet led to the increases in cortical gene expression of TGF-beta 1, LTBP, and TGF-beta receptors, compared with the LS diet. The glomerular biosynthesis of fibronectin and plasminogen activator inhibitor-1 (PAI-1), and cortical mRNA expression for fibronectin, collagen I, and PAI-1 (which may be affected by TGF-beta) in the HS rats were elevated, compared with the LS rats. The latent TGF-beta immunostained by anti-LTBP antibody was localized on the sclerosing glomeruli and vascular walls. Furthermore, fibronectin, collagen I, and PAI-1 were also localized in the sclerotic area. The TGF-beta 1-positive cells, immunostained by antibody for latency-associated peptide of TGF-beta 1, increased in the glomeruli and vascular walls in the HS rats. These results thus suggested that TGF-beta 1 may be related to hypertensive renal injury in this model.
 ...
PMID:Transforming growth factor-beta 1 in hypertensive renal injury in Dahl salt-sensitive rats. 898 36

Hypertension is often accompanied by a variety of metabolic abnormalities. These metabolic abnormalities include insulin resistance, dyslipidemia and abnormalities of the coagulation-fibrinolytic system predisposing to a procoagulent state. The nexus for all of these abnormalities may be central (visceral) obesity. The dyslipidemia accompanying hypertension consists of low HDL cholesterol, elevated triglyceride levels and an abnormal more atherogenic LDL cholesterol particle. Dyslipidemia interacts with associated hemodynamic (ie, hypertension) and metabolic (ie, increased platelet aggregation and PAI-1 levels) in a multiplicative manner potentiating cardiovascular and renal disease. Accordingly, lipid therapy should be aggressive to attenuate these medical complications of essential hypertension.
 ...
PMID:Impact of lipid and ACE inhibitor therapy on cardiovascular disease and metabolic abnormalities in the diabetic and hypertensive patient. 911 Nov 51

An abnormality in platelet aggregability or fibrinolysis, namely elevated activity of plasminogen activator inhibitor-1 (PAI-1), has been recently documented in patients suffering from Klinefelter's syndrome associated with leg ulceration without underlying venous insufficiency. To determine whether increased PAI-1 activity is a general feature of Klinefelter's syndrome, or more specifically associated with leg ulceration, we investigated PAI-1 influencing parameters and PAI-1 activity in two groups of patients: (i) Klinefelter patients suffering from leg ulceration (n = 7); and (ii) Klinefelter patients without leg ulceration (n = 6). On analysing PAI-1 influencing parameters such as age, body mass index, triglycerides, C-reactive protein, testosterone, smoking behaviour, the presence of diabetes mellitus, and arterial hypertension, respectively, we found no statistically significant differences between the two groups. However, PAI-1 activity in group 1 was highly significantly elevated compared with that in group two patients (P < 0.005). We conclude that (i) PAI-1 activity is not elevated in Klinefelter's syndrome in general; (ii) elevation of PAI-1 activity in patients suffering from Klinefelter's syndrome does not appear to be secondary to PAI-1 influencing parameters; and (iii) elevation of PAI-1 activity may play a crucial role in the pathogenesis of leg ulceration in Klinefelter's syndrome. Therefore, a therapy for leg ulceration in Klinefelter's syndrome that aims to return the elevated PAI-1 activity to normal should be explored.
 ...
PMID:Leg ulcers in Klinefelter's syndrome--further evidence for an involvement of plasminogen activator inhibitor-1. 911 12

Clustering of risk factors for cardiovascular disease related to insulin resistance may account for the increased incidence of vascular disease in these conditions and in non-diabetic subjects. To investigate the relationship between a coding polymorphism in the insulin receptor substrate-1 gene and the presence of cardiovascular risk factors, 209 patients with NIDDM and 452 subjects investigated for coronary artery disease (CAD) were studied. In the NIDDM subjects 22 (10.5%) were heterozygous at codon 972 for a polymorphism which codes for a glycine to arginine substitution and 187 (89.5%) were homozygous for the wild type. Patients with the mutation had lower levels of cholesterol compared with wild type (mean, 95% confidence intervals), 5.3 (4.9-5.8) vs 6.0 (5.9-6.2) mmol/l, respectively (P = 0.002), triglyceride 1.7 (1.4-2.1) vs 2.2 (2.0-2.4) mmol/l (P = 0.051), factor VII:C activity 109.5 (85.5-133.5) vs 133.5 (127-140)% (P = 0.057) and PAI-1 antigen, 16.0 (10.5-24.3) vs 22.2 (20.0-24.6) ng/ml (P = 0.054). There were no differences in body mass index, indices of glycaemic control, fasting insulin or the prevalence of hypertension. In patients with CAD, 55 (12.7%) were carriers of the mutation (including three homozygotes) (NIDDM vs CAD, NS). Although similar trends in cholesterol, factor VII, PAI-1 antigen and triglyceride existed between carriers of the mutation and the wild type, none reached statistical significance. The results indicate that the IRS-1 gene is not implicated in the pathogenesis of NIDDM or CAD.
 ...
PMID:Insulin receptor substrate-1 gene polymorphism and cardiovascular risk in non-insulin dependent diabetes mellitus and patients undergoing coronary angiography. 921 52

It has been suggested that impaired fibrinolytic-coagulation system, such as increased concentration of inhibitors to fibrinolysis or activators to coagulations, occasionally may play a role in the development of atherosclerotic vascular disease. In this study, we aimed to elucidate the relationship of serum lipids to fibrinolytic-coagulation system. The subjects studied were 190 outpatients at Kyorin University Hospital, 108 of whom were mostly hypertension, diabetes mellitus and hyperuricemia (Control), 59 of whom were coronary heart disease (CHD), 25 of whom were cerebrovascular disease (CVD). Blood samples were measured the levels of blood coagulation factors VII (F-VII) and X (F-X), and plasminogen activator inhibitor-1 (PAI-1) in these subjects, together with the concentrations of serum lipids. The serum levels of F-X was significantly higher in CHD subjects than in controls (111 +/- 19% vs 101 +/- 22%, p < 0.05). However, there was a no significant difference of F-VII among three groups. And we found that the levels of serum lipids, especially serum triglycerides showed a significant positive correlation between the concentrations of F-VII (r = 0.343, p < 0.01) and F-X (r = 0.513, p < 0.01), and PAI-1 (r = 0.528, p < 0.001) in CHD and CVD subjects. For this reason, 156 bank employee subjects were also admitted to this study (Bank employees). In bank employee subjects, the serum levels of triglycerides also showed a significant positive correlation with the levels of F-VII (r = 0.321, p < 0.001), F-X (r = 0.254, p < 0.001) and PAI-1 (r = 0.420, p < 0.001). These data suggest that serum lipids, particularly triglycerides have a close relationship with thrombogenesis as evidenced by activated F-VII and F-X in the extrinsic coagulation system and also by elevated PAI-1 activities in fibrinolysis. Therefore, when we try to prevent the patients from CHD or treat them, we ought pay attentions not only to serum cholesterol or LDL-cholesterol for their atherogenic actions, but also to triglycerides because of their close correlation with extrinsic coagulation system and anti-fibrinolytic activities. The reduction of fibrinolytic capacity due to increased plasma levels of F-VII, X and PAI-1 may have importance in atherosclerotic vascular disease, particularly in patients with hypertriglyceridemia.
 ...
PMID:Serum triglycerides and blood coagulation factors VII and X, and plasminogen activator inhibitor-1. 922 31

In twenty patients with primitive venous hypertension and in ten healthy subjects we have determined the plasmatic levels of: Thrombomodulin (TM), beta-Thromboglobulin (beta-TG), D-Dimer (DD), the tissue activator of the plasminogen (t-PA) and the inhibitor of the activator of the plasminogen (PAI-1). The levels of the parameter we studied have shown in the patients a significant difference of beta-TG (p < 0.01) and PAI-1 (p < 0.01) compared to the controls, whereas there was no significant difference in the other parameters we studied. Our data underline, in patients with primitive venous hypertension, the importance that the activation of the platelets and the reduction of the potential fibrinolytic can assume, together with the stasis, regarding the onset of thrombotic complications.
 ...
PMID:Haemostatic parameters in patients with primitive venous hypertension. 923 Jun 18

This study was aimed at investigating haemostasis parameters in patients (pts) with arterial hypertension (AH) before any medical treatment and to correlate these findings with those in healthy normal Greek population 83 pts (48 m, 35 w) mean age 49.8 +/- 10.1 yrs, body mass index 23.4 +/- 1.5 with mild to moderate AH and 42 healthy volunteers matched for sex (24 m, 18 w), age 51.2 +/- 10.5 yrs and body mass index 22.8 +/- 1.46 were studied. Fibrinogen, vWF, plasminogen, ECLT, a2 antiplasmin, tPA-Ag, PAI-1 in all pts and in the control group were measured. Mean age and BMI did not significantly differ between the two groups. The hypertensive patients had significantly higher levels of fibrinogen (327.75 +/- 51.36 vs. 272.84 +/- 46.8 mg/dl), tPA-Ag (8.81 +/- 3.32 vs. 5.76 +/- 2.54 ng/ml) and PAI-1 (11.8 +/- 10.9 vs. 7.91 +/- 5.5 IU/ml), whereas a2 antiplasmin level was significantly lower (98.71 +/- 15.40 vs. 107.84 +/- 17.52%). No differences were found between hypertensives and normal subjects in vWF, plasminogen and ECLT. These preliminary data suggest that in pts with mild to moderate AH, before any medical treatment, there are significantly higher levels of fibrinogen, tPA-Ag and PAI-1 compared with normal volunteers, whereas there are significantly lower a antiplasmin levels. These findings indicate a disturbance in the haemostasis balance with hypercoagulability and fibrinolytic deficiency.
 ...
PMID:Haemostasis balance disorders in patients with essential hypertension. 936 64


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>