UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vascular smooth muscle cell (SMC) proliferation is a key event in the development of (spontaneous) atherosclerosis, hypertension-related arteriosclerosis, angioplasty-induced restenosis and venous bypass graft arteriosclerosis. Many factors or environmental stimuli are believed to be responsible for SMC growth or hypertrophy in the vessel wall. How these environmental stimuli or signals applied onto the surface of SMCs are transduced into the cell nucleus resulting in quantitative and qualitative changes in gene expression in SMCs of arterial walls is largely unknown. Mitogen-activated protein (MAP) kinases are rapidly activated in cells stimulated with various extracellular signals by dual phosphorylation of tyrosine and threonine residues. They are thought to play a pivotal role in transmitting transmembrane signals required for cell growth and differentiation. Recent studies have focused on the signalling events in vascular tissues in vivo and in cultured SMCs in vitro. It has been demonstrated that acute hypertension and angioplasty rapidly induced MAP kinase activation in the arterial wall. Kinase activation is followed by an increase in c-fos and c-jun gene expression and enhanced transcription factor AP-1 DNA-binding activity. A similar MAP kinase activation can be mimicked in in vitro cultured SMCs stimulated by either shear stress or cyclic strain stretch, suggesting direct effects of mechanical force. Interestingly, physical forces rapidly resulted in phosphorylation of platelet-derived growth factor (PDGF) receptor, an activated state, in cultured SMCs. Thus, mechanical stresses may directly perturb the cell surface or alter receptor conformation, thereby initiating signalling pathways usually used by growth factors. These findings have significantly enhanced our knowledge concerning the pathogenesis of arteriosclerosis and provide a basis for therapeutic intervention on vascular diseases.
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PMID:Signal transduction in arteriosclerosis: mechanical stress-activated MAP kinases in vascular smooth muscle cells (review). 985 3

An alanine to threonine substitution at codon 54 of the fatty acid binding protein 2 (FABP2) gene has been associated with insulin resistance in Pima Indians and with obesity in aboriginal Canadians. We investigated whether this polymorphism contributes to obesity and insulin resistance in 258 Japanese subjects. Thirty-six subjects (13.9%) were homozygous for the Thr54 allele, 106 (41.1%) were heterozygous for the Ala54/Thr54 allele, and 116 (45.0%) were homozygous for the Ala54 allele. The frequency of the Thr54 allele was 0.34 and did not differ significantly between men and women. The incidence of non-insulin-dependent diabetes mellitus (NIDDM) was not different among the three genotypes. The variation at codon 54 of the FABP2 gene was not associated with obesity, hypertension, dyslipidemia, hyperuricemia, or hyperinsulinemia. These results suggest that the polymorphism at codon 54 of the FABP2 gene is not a major contributing factor to obesity and insulin resistance in Japanese subjects.
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PMID:Variation of the fatty acid binding protein 2 gene is not associated with obesity and insulin resistance in Japanese subjects. 1033 70

A missense gene mutation with methione-to-threonine amino acid substitution at codon 235 (M235T) of angiotensinogen (AGT) has been associated with higher plasma AGT levels and may influence the pathogenesis of cardiac hypertrophy and atherosclerosis. This study was undertaken to investigate the relationship of the M235T polymorphism of the AGT gene with left ventricular mass (LVM) and carotid intima-media thickness (IMT) in 175 Chinese patients with hypertension. The M235T mutation was detected by a mispairing primer method to create a BstUI restriction site in the polymerase chain reaction. The LVM was calculated with M-mode echocardiographic measures of the left ventricle. The IMT was measured in the common carotid and carotid bifurcation by B-mode ultrasound. Patients with the TT genotype (n = 106) were found to have significantly greater LVM index than those with the MM (n = 32) and MT (n = 37) genotypes (129.2 +/- 34.3 v 112.5 +/- 38.3 and 107.4 +/- 30.0 g/m2, P = .002), but the carotid IMT showed insignificant differences among three genotypic groups (1.320 +/- 0.703, 1.349 +/- 0.777, and 1.309 +/- 0.797 mm, P = .97). The M235T polymorphism (P = .004) was a significant predictor for LVM on multiple regression analysis, controlling all the potential confounding factors including age (P = .04), gender (P = .000), body mass index (P = .000), and so on, but the carotid IMT correlated only with age (P = .000), smoking (P = .02), and tissue plasminogen activator antigen (P = .02). These results indicated that the TT genotype of the AGT gene could be considered a risk factor for the development of cardiac hypertrophy, but not for carotid atherosclerosis in the hypertensive population.
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PMID:Left ventricular mass, carotid wall thickness, and angiotensinogen gene polymorphism in patients with hypertension. 1034 81

The contribution of genetic factors to hypertension in pregnancy, including pre-eclampsia, has been well documented. The association with a common molecular variant of the angiotensinogen (AGT) gene, in which methionine (M235) is substituted for threonine (T235) at residue 235, has been reported in both Caucasians and Japanese. In the present study, we examined 115 cases of pure type of hypertension in pregnancy (PHP) and 381 normal pregnant controls in order to look for subgroups in which the AGT gene is the major factor in the PHP pathogenesis. By classification of PHP cases according to the clinical diagnosis, gravidity, and maternal age, we found significantly higher frequencies of T235 in both all PHP patients and preeclampsia/eclampsia patients than in normal controls. These results are discordant with those reported for Caucasian subjects where only a group of preeclamptic primigravidae was associated with the AGT variant, possibly indicating the existence of a racial difference. We also found that the variant frequency was significantly higher in the PHP subgroup with maternal age of 20-34 years (0.93) than in a subgroup of multigravid PHP patients age 35 years or older (0.77, P < 0.05) or in normal controls of age 20-34 years (0.76, P < 0.001). The result indicates that the AGT variant plays a significant role in hypertension in the age group 20-34 years.
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PMID:Association of a variant of the angiotensinogen gene with pure type of hypertension in pregnancy in the Japanese: implication of a racial difference and significance of an age factor. 1048 71

Hemodynamic factors, circulating hormones, paracrine factors, and intracrine factors influence vascular smooth muscle growth and plasticity. The well-characterized role of angiotensin II in the modulation of vascular tone and cell function may be critically involved in the mechanisms by which vascular smooth muscle responds to signals associated with vascular endothelial dysfunction and increases in oxidative stress. Studies from this laboratory suggest that the trophic actions of angiotensin II may be intrinsically regulated by angiotensin-(1-7), a separate product of the angiotensin system derived from the common substrate, angiotensin I. Exposure of cultured vascular smooth muscle cells to angiotensin-(1-7) inhibited the trophic actions of angiotensin II and reduced the expression of the mitogenic effects of both normal serum and platelet-derived growth factor. The growth-inhibitory actions of angiotensin-(1-7) were blocked by the selective D-alanine(7)-angiotensin-(1-7) antagonist and the nonselective angiotensin receptor blocker sarcosine(1)-threonine(8)-angiotensin II. In contrast, subtype-selective antagonists for the AT(1) and AT(2) receptors had no effect on the inhibitory actions of angiotensin-(1-7), a finding that is consistent with the pharmacological characterization of a high-affinity (125)I-labeled angiotensin-(1-7) binding site in the vasculature by use of selective and nonselective angiotensin II receptor antagonists. The relevance of these findings to the proliferative response of vascular smooth muscle cells after endothelial injury was confirmed by assessment of the effect of a 12-day infusion of angiotensin-(1-7) on neointimal formation. In these experiments, the proliferative response produced by injuring the carotid artery was inhibited by angiotensin-(1-7) through a mechanism that could not be explained by changes in arterial pressure. Because plasma angiotensin-(1-7) increased to levels comparable to those found in animals and human subjects given therapeutic doses of angiotensin-converting enzyme inhibitors, angiotensin-(1-7) may be one factor participating in the reversal of vascular proliferation during inhibition of angiotensin II formation or activity.
Hypertension 1999 Oct
PMID:State-of-the-Art lecture. Antiproliferative actions of angiotensin-(1-7) in vascular smooth muscle. 1052 90

Maternal protein deficiency during pregnancy is associated with changes in glucose tolerance and hypertension in the offspring of rats. In this study the growth of rat fetuses was examined when the dams were fed diets containing 18% casein, 9% casein or 8% casein supplemented with threonine. The extra threonine was added to reverse the decrease in circulating threonine concentrations that occurs when pregnant rats are fed protein-deficient diets. The fetuses of the group fed the low protein diet supplemented with threonine were significantly smaller than those of the control group and not significantly different from those fed low protein. Homogenates prepared from the livers of dams fed the diet containing 9% casein oxidized threonine at approximately twice the rate of homogenates prepared from dams fed the diet containing 18% casein. We conclude that circulating levels of threonine fall as a consequence of an increase in the activity of the pathway that metabolizes homocysteine produced by the transulfuration of methionine. Serum homocysteine was unaffected in the dams fed low protein diets compared with controls, but was significantly greater in dams fed the low protein diet supplemented with threonine. Elevated levels of homocysteine are associated with changes in the methylation of DNA. The endogenous methylation of DNA was greater than that of controls in the livers of fetuses from dams fed the 9% protein diets and increased further when the diet was supplemented with threonine. Our results suggest that changes in methionine metabolism increase homocysteine production, which leads to changes in DNA methylation in the fetus. An increase in maternal homocysteine may compromise fetal development, leading to the onset of glucose intolerance and hypertension in adult life.
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PMID:Maternal protein deficiency causes hypermethylation of DNA in the livers of rat fetuses. 1086 57

Several studies have demonstrated an association of CTLA4 (IDDM12) alanine-17 with type 1 diabetes, but CTLA4 variants have not yet been investigated in type 2 diabetes. The CTLA4 exon 1 polymorphism (49 A/G) was analyzed in 300 Caucasian patients with type 2 diabetes and 466 healthy controls. All patients were negative for glutamate decarboxylase and islet cell antibodies. CTLA4 alleles were defined by PCR, single-strand conformational polymorphism, and restriction length fragment polymorphism analysis using BBV:I. The distribution of alleles as well as the genotypic and phenotypic frequencies were similar among patients and controls [AA, 42 vs. 39%; AG, 47 vs. 46%; GG, 11 vs. 15%, P = not significant (n.s.); A/G, 65/35% vs. 62/38%, P = n.s.; alanine/threonine 92/58% vs. 85/61%, P = n.s.]. However, detailed analysis of clinical and biochemical parameters revealed a tendency of GG (alanine/alanine) toward younger age at disease manifestation (46.8 +/- 0.8 vs. 49.5 +/- 0.8 yr, mean +/- SEM), lower body mass index (21.4 +/- 0.5 vs. 24.4 +/- 0.5 kg/m(2), P = 0.042), and basal C-peptide level (0.33 +/- 0.07 vs. 0.53 +/- 0.07nmol/L), as well as earlier start of insulin treatment (5.8 +/- 1.2 vs. 8.7 +/- 0.6 yr) and higher portion of patients on insulin (71 vs. 61%). Patients with the AA genotype were significantly less likely to develop microangiopathic lesions (P < 0.0005). No differences were found for hypertension or family history of type 2 diabetes. In conclusion, CTLA4 alanine-17 does not represent a major risk factor for type 2 diabetes. Additional studies on larger groups and different ethnic groups are warranted to clarify the association of the GG genotype with faster ss-cell failure and the lower rate of microvascular complications in AA carriers.
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PMID:The codon 17 polymorphism of the CTLA4 gene in type 2 diabetes mellitus. 1115 25

A common variant at codon 235 of the angiotensinogen gene with methionine to threonine amino acid substitution (AGT M235T) has been reported as a genetic risk for essential hypertension. However, the frequency of AGT T235 was heterogeneous among races, and a positive association between AGT M235T and hypertension was not settled. To examine the association in a general population of Japanese (n=4013), we introduced the TaqMan polymerase chain reaction method and examined the relation between hypertension and T+31C polymorphism, which was in absolute linkage disequilibrium with AGT M235T. The C+31 allele of AGT was significantly associated with the positive family history of hypertension (FH) but not with the presence of hypertension or blood pressure. The subjects with CC tended to have hypertensive relatives, especially a hypertensive father or siblings, and its statistical significance was stronger in men. Adjustment of confounding factor did not alter the results of simple association study, suggesting that this positive association with FH is independent and significant. Our findings revealed that the TaqMan polymerase chain reaction method is a powerful tool for genetic association study with a large number of subjects and that AGT T+31C is significantly associated with paternal FH.
Hypertension 2001 Feb
PMID:T+31C polymorphism of angiotensinogen gene and essential hypertension. 1123 Feb 86

Genetic variability in the renin angiotensin system may modify renal responses to injury and disease progression. We therefore examined whether the insertion/deletion polymorphism of the angiotensin-converting enzyme (ACE) gene, the Met235-->Thr polymorphism of the angiotensinogen (AGT) gene, and the A1166-->C polymorphism of the angiotensin II type 1 receptor gene (ATR1) were associated with disease progression and outcome after renal transplantation (Tx) in 100 Caucasian pediatric renal transplant recipients. The observed allele frequencies were: DD 31%, DI 41% and II 28%, for ACE; MM 42%, MT 37% and TT 21%, for the methionine (Met)235-->threonine (Thr) polymorphism of AGT; and AA 51%, AC 38% and CC 11%, for the adenine (A)1166-->cytosine (C) gene polymorphism. The slope of 1/creatinine was determined by linear regression analysis of a median of 12 points before and after renal Tx, and the population was divided in two equal groups, according to the slope, both before and after Tx. There were no statistically significant differences for AGT, ACE, and ATR1 polymorphisms with regard to the slope of 1/creatinine before renal Tx. After renal Tx, the ACE II genotype (p = 0.024, chi-square test) and the presence of the I allele (p=0.033, chi-square test) were associated with a favorable slope of 1/creatinine. There was no association of the AGT or the ATR1 polymorphism with outcome after renal Tx, and none of the genotypes were associated with hypertension before or after renal Tx. We suggest that the beneficial association of disease progression after renal Tx with the II genotype and/or the presence of the I allele in our pediatric cohort might be explained by a lower activity of the circulating ACE enzyme associated with the I allele.
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PMID:Renin angiotensin system gene polymorphisms in pediatric renal transplant recipients. 1142 18

Many recent case-control studies have suggested a significant relationship between M235T (the substitution of threonine for methionine at position 235 codon) polymorphism of the angiotensinogen (AGT) gene and hypertension. To investigate whether the M235T polymorphism of AGT gene affects the incidence of hypertension, a retrospective cohort study was performed among Japanese workers. The subjects were Japanese workers at an occupational site in Shimane Prefecture in Japan. The baseline data were set at the received regular health examination in 1992, and a retrospective cohort study was performed for analyzing the incidence of hypertension in 1998. The rates of M235M (MM), M235T (MT) and T235T (TT) genotypes were 4%, 32% and 64%, respectively. The relative risks of MT and TT against MM for the incidence of hypertension by single variance analysis were 1.47 [95% confidence interval (CI) 0.50 - 4.33] and 1.35 (95% CI 0.47 - 3.90), respectively. The relative risks of MT and TT against MM for the incidence of hypertension, adjusted for sex, age, body mass index, fasting glucose and cigarette smoking, drinking and exercise in 1992, were 1.49 (95% CI 0.49 - 4.53) and 1.25 (95% CI 0.42 3.74), respectively. The data from this study suggest that the M235T polymorphism of AGT gene has a weak role in the manifestation of hypertension. Further comprehensive studies are needed to resolve this issue.
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PMID:Angiotensinogen gene variation and hypertension in a cohort study in Japanese. 1143 22

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