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)

In a prospective, blind study of 183 unselected women attending for routine booking scan with a singleton pregnancy at 16-24 weeks' gestation, uteroplacental resistance index, and peripheral levels of alpha-fetoprotein, human chorionic gonadotropin, human placental lactogen, Schwangerswaft protein, pregnancy-associated placental protein A and insulin-like growth factor (IGF) binding protein 1 were measured. High levels of alpha-fetoprotein and IGF 1 binding protein 1 (> 90th centile) were associated with small-for-gestational age babies (< 10th centile) (sensitivity 24% and 22%; specificity 90% and 91%). High levels of alpha-fetoprotein, human chorionic gonadotropin and pregnancy-associated placental protein A (> 90th centile) were associated with one or more of three severe complications of pregnancy: very small-for-gestational age (< 3rd centile), severe proteinuric hypertension or intrauterine death (sensitivity 20%, 20% and 57%; specificity 90%, 95% and 91%, respectively). A uteroplacental resistance index > 90th centile was also associated with small-for-gestational age and severe complications (sensitivity 24% and 50%, specificity 90% and 90%). A combination of resistance index and a placental function test improved the prediction for a group of patients that included any complications (sensitivity 31% and specificity 89%). Doppler ultrasound was a more efficient predictor than individual placental function tests but screening predictions can be improved by combining Doppler parameters and placental protein estimations. Combinations of placental function tests might provide equivalent, or complementary, information. This preliminary work demonstrates the potential value of combining biophysical and biochemical tests to predict complications of pregnancy.
 ...
PMID:Early prediction of uteroplacental complications of pregnancy using Doppler ultrasound, placental function tests and combination testing. 1279 32

Diabetes mellitus and hypertension are often associated with each other, and both are risk factors for cardiovascular diseases. Insulin resistance has been noted as an etiology for diabetes, hypertension and atherosclerosis. Insulin resistance often accompanied hyperinsulinemia and it is thought to elevate blood pressure through stimulation of the sympathetic nervous system and renin-angiotensin system, promotion of sodium retention in the renal tubules, and proliferation of vascular smooth muscle cells via insulin-like growth factor. Also high blood glucose may impair vascular endothelial cells and produce oxidant stress. To prevent the occurrence of hypertension in diabetes patients, improving insulin resistance have to be considered, and primary care such as reducing body weight, salt and alcohol restriction, exercise and non-smoking are important.
 ...
PMID:[How to prevent the incidence of hypertension in type 2 diabetes patients]. 1287 77

1. We investigated the mechanisms underlying the changes in vascular contractile responsiveness induced by chronic treatment with insulin in controls and established streptozotocin (STZ)-induced diabetic rats. 2. The aortic contractile response to noradrenaline (NA) showed no significant difference between controls and diabetics, but it was significantly greater in insulin-treated diabetic rats than in the other groups. To investigate the mechanism, we examined the changes in NA-induced contractility following treatment with insulin and insulin-like growth factor-1 (IGF-1) in organ-cultured control and diabetic aortas. 3. The contractile response to NA in organ-cultured diabetic rat aortas treated with insulin (500 ng ml-1, 16 h) or IGF-1 (20 ng ml-1, 16 h) was significantly greater than the corresponding values for (a) diabetic rat aortas cultured in serum-free medium, and (b) control aortas incubated with insulin or IGF-1. Incubating control aortas with insulin or IGF-1 had no significant effect on the contraction induced by NA. 4. The expressions of the IGF-1 receptor mRNA and protein were increased in STZ-induced diabetic aortas and further increased in insulin-treated diabetics. The mRNA expressions of IGF-binding protein (IGFBP)-2 and IGFBP-3 were normal in diabetic aortas. In contrast, those of IGFBP-4 and IGFBP-5 were significantly decreased in diabetic aortas, and not restored by insulin treatment. 5. These results suggest that the insulin deficiency and chronic hyperinsulinemia in diabetes upregulate the IGF-1 receptor and downregulate IGFBP-4 and IGFBP-5 in the aorta. This may be a major cause of the increased vascular contractility induced by insulin administration and by hyperinsulinemia in established diabetes, resulting in hypertension.
 ...
PMID:Possible involvement of IGF-1 receptor and IGF-binding protein in insulin-induced enhancement of noradrenaline response in diabetic rat aorta. 1297 Jan 7

Compensatory hyperinsulinemia stemming from peripheral insulin resistance is a well-recognized metabolic disturbance that is at the root cause of diseases and maladies of Syndrome X (hypertension, type 2 diabetes, dyslipidemia, coronary artery disease, obesity, abnormal glucose tolerance). Abnormalities of fibrinolysis and hyperuricemia also appear to be members of the cluster of illnesses comprising Syndrome X. Insulin is a well-established growth-promoting hormone, and recent evidence indicates that hyperinsulinemia causes a shift in a number of endocrine pathways that may favor unregulated tissue growth leading to additional illnesses. Specifically, hyperinsulinemia elevates serum concentrations of free insulin-like growth factor-1 (IGF-1) and androgens, while simultaneously reducing insulin-like growth factor-binding protein 3 (IGFBP-3) and sex hormone-binding globulin (SHBG). Since IGFBP-3 is a ligand for the nuclear retinoid X receptor alpha, insulin-mediated reductions in IGFBP-3 may also influence transcription of anti-proliferative genes normally activated by the body's endogenous retinoids. These endocrine shifts alter cellular proliferation and growth in a variety of tissues, the clinical course of which may promote acne, early menarche, certain epithelial cell carcinomas, increased stature, myopia, cutaneous papillomas (skin tags), acanthosis nigricans, polycystic ovary syndrome (PCOS) and male vertex balding. Consequently, these illnesses and conditions may, in part, have hyperinsulinemia at their root cause and therefore should be classified among the diseases of Syndrome X.
 ...
PMID:Hyperinsulinemic diseases of civilization: more than just Syndrome X. 1452 33

The vascular insulin-like growth factor (IGF)-1 system includes the IGFs, the IGF-1 receptor (IGF-1R), and multiple binding proteins. This growth factor system exerts multiple physiologic effects on the vasculature through both endocrine and autocrine/paracrine mechanisms. The effects of IGF-1 are mediated principally through the IGF-1R but are modulated by complex interactions with multiple IGF binding proteins that themselves are regulated by phosphorylation, proteolysis, polymerization, and cell or matrix association. During the last decade, a significant body of evidence has accumulated, indicating that expression of the components of the IGF system are regulated by multiple factors, including growth factors, cytokines, lipoproteins, reactive oxygen species, and hemodynamic forces. In addition, cross-talk between the IGF system and other growth factors and integrin receptors has been demonstrated. There is accumulating evidence of a role for IGF-1 in multiple vascular pathologies, including atherosclerosis, hypertension, restenosis, angiogenesis, and diabetic vascular disease. This review will discuss the regulation of expression of IGF-1, IGF-1R, and IGF binding proteins in the vasculature and summarize evidence implicating involvement of this system in vascular diseases.
 ...
PMID:Expression, regulation, and function of IGF-1, IGF-1R, and IGF-1 binding proteins in blood vessels. 1460 34

Left ventricular (LV) mass that develops as cardiac adaptive remodeling represents a powerful independent predictor of cardiovascular morbidity and mortality in the general population and in several clinical conditions, including essential hypertension. However, many studies have shown that blood pressure explains only 10% to 25% of the variation in LV mass, supporting the hypothesis that other factors, such as genetics or metabolics (insulin-resistance/hyperinsulinemia), are involved in the cardiac growth in human hypertension. Essential hypertension is also characterized by insulin-resistance/hyperinsulinemia, which may directly induce LV hypertrophy through the stimulation of insulin-like growth factor-1 receptors, abundantly expressed in myocardium. Taken together, we investigated the growth effect of fasting insulin, associated with angiotensin-converting enzyme-gene polymorphism, on cardiac mass in a group of previously untreated hypertensive patients.
 ...
PMID:Relation of fasting insulin related to insertion/deletion polymorphism of angiotensin-converting enzyme-gene and cardiac mass in never-treated patients with systemic hypertension. 1460 9

Recent evidence indicates that mutations in the gene encoding the WNK1 [with no K (lysine) protein kinase-1] results in an inherited hypertension syndrome called pseudohypoaldosteronism type II. The mechanisms by which WNK1 is regulated or the substrates it phosphorylates are currently unknown. We noticed that Thr-60 of WNK1, which lies N-terminal to the catalytic domain, is located within a PKB (protein kinase B) phosphorylation consensus sequence. We found that PKB phosphorylated WNK1 efficiently compared with known substrates, and both peptide map and mutational analysis revealed that the major PKB site of phosphorylation was Thr-60. Employing a phosphospecific Thr-60 WNK1 antibody, we demonstrated that IGF1 (insulin-like growth factor) stimulation of HEK-293 cells induced phosphorylation of endogenously expressed WNK1 at Thr-60. Consistent with PKB mediating this phosphorylation, inhibitors of PI 3-kinase (phosphoinositide 3-kinase; wortmannin and LY294002) but not inhibitors of mammalian target of rapamycin (rapamycin) or MEK1 (mitogen-activated protein kinase kinase-1) activation (PD184352), inhibited IGF1-induced phosphorylation of endogenous WNK1 at Thr-60. Moreover, IGF1-induced phosphorylation of endogenous WNK1 did not occur in PDK1-/- ES (embryonic stem) cells, in which PKB is not activated. In contrast, IGF1 still induced normal phosphorylation of WNK1 in PDK1(L155E/L155E) knock-in ES cells in which PKB, but not S6K (p70 ribosomal S6 kinase) or SGK1 (serum- and glucocorticoid-induced protein kinase 1), is activated. Our study provides strong pharmacological and genetic evidence that PKB mediates the phosphorylation of WNK1 at Thr-60 in vivo. We also performed experiments which suggest that the phosphorylation of WNK1 by PKB is not regulating its kinase activity or cellular localization directly. These results provide the first connection between the PI 3-kinase/PKB pathway and WNK1, suggesting a mechanism by which this pathway may influence blood pressure.
 ...
PMID:WNK1, the kinase mutated in an inherited high-blood-pressure syndrome, is a novel PKB (protein kinase B)/Akt substrate. 1461 43

Administration of glucocorticoids results in hypertension, cardiac hypertrophy, and general myopathy. The present study analyzed the acute effect of dexamethasone (0.5 mg/100 g for 3 days) or dexamethasone plus insulin-like growth factor-1 (0.35 mg/100 g for 3 days) on differential gene expression in the gastrocnemius muscle and the left ventricular myocardium of rats. Dexamethasone induced atrophy of gastrocnemius muscle. Cathepsin L, and not ubiquitin, was the earliest mediator of skeletal muscle proteolysis induced by dexamethasone. Insulin-like growth factor-1 reversed gastrocnemius muscle mass, and deleted a part of downregulated genes by dexamethasone. On the other hand, dexamethasone administration did not result in cardiac hypertrophy or hypertension. Only prostaglandin D synthase gene was upregulated by dexamethasone in myocardium, and genes related to extracellular matrix and proteinase inhibitor were downregulated. Molecular alteration for hypertrophy might have initiated. Dexamethasone-induced proteolysis and reversal with insulin-like growth factor-1 occurred rapidly in skeletal muscle; but was relatively delayed in the myocardium.
 ...
PMID:Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: analysis by microarray. 1461 91

Cross-sectional studies have found associations between components of the insulin-like growth factor (IGF) system and hypertension, total cholesterol, and low density lipoprotein cholesterol. Using partial correlation analysis and longitudinal analysis of data collected at the year 2, year 7, and year 10 examinations, the authors assessed the associations of IGF-1 and IGF binding protein-3 (IGFBP-3) with cardiovascular disease risk factors in 544 Black and 747 White male participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Male Hormone Study who were aged 20-34 years at year 2 (1987-1988). There were no consistent independent associations with blood pressure. Cross-sectionally, there were some inverse associations between IGF-1 and lipid levels in White men (strongest r = -0.095 (p = 0.02) for total cholesterol at year 7) and positive associations between IGFBP-3 and lipid levels in Black and White men (for log(triglycerides), r = 0.072-0.136). Longitudinally, a 1,000-ng/ml increase in IGFBP-3 was associated with 3.7-mg/dl and 2.6-mg/dl higher total cholesterol levels and 2.6-mg/dl and 1.7-mg/dl higher low density lipoprotein cholesterol levels in Black men and White men (p < 0.05), respectively. These findings do not support a strong link between IGF-1 and IGFBP-3 and blood pressure, but they do support the possibility of important relations between IGFBP-3 and lipid levels in young adult men.
 ...
PMID:Insulin-like growth factor-1, insulin-like growth factor binding protein-3, and cardiovascular disease risk factors in young black men and white men: the CARDIA Male Hormone Study. 1546 97

A case of symptomatic Rathke's cleft cyst and growth hormone (GH) secreting pituitary adenoma is described. A patient presented with a visual field deficit and a brain magnetic resonance imaging (MRI) study demonstrated compression of the optic chiasm by a large suprasellar cyst and a small lesion in the sellar consistent with a microadenoma. Preoperative clinical evaluation revealed mild acromegalic features, glucose intolerance, hypertension, hypercholesterolemia, and carpel tunnel syndrome, and blood testing confirmed an elevated insulin-like growth factor-1 (IGF-1). A modified transsphenoidal skull based approach was performed for selective transsphenoidal adenomectomy and decompression of the surprasellar cyst. The patient had an uneventful postoperative course with resolution of the visual field deficits and dysmenorrhea. Endocrine testing at two-month post procedure were normal. While there have been a small number of cases reported of concomitant pituitary adenomas and Rathke's cleft cysts, there is no report known to these authors of coexisting symptomatic lesions.
 ...
PMID:Simultaneous symptomatic Rathke's cleft cyst and GH secreting pituitary adenoma: a case report. 1563 97


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