Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Complete ureteral obstruction in rats rapidly leads to renal interstitial expansion and fibrosis and this process is ameliorated by concomitant angiotensin converting enzyme inhibition (ACEI). However, models of intervention initiated after unilateral ureteral obstruction (UUO) release may be more analogous to human obstructive renal disease where treatment could more reasonably follow the discovery of obstructive uropathy as compared to models where treatment is initiated at the time of experimentally induced obstruction. We studied interstitial changes in rats before and after release of UUO and examined the effect of ACEI with 200mg/L of enalapril (E) in the drinking water on these changes. Rats were sacrificed after 10 (n=10) and 20 (n=10) days (D) of UUO or 10D after release of 10D of UUO (n=18). Eleven rats received E for 10D after UUO release. Cortical interstitial volume fraction [Vv(I/C)] measured by point counting was increased at 10D (0.32 +/- 0.05) and 20D (0.41 +/- 0.05) of UUO compared to contralateral and sham-operated kidneys (both 0.05 +/- 0.01, ANOVA, p <0.001). Vv(I/C) 10D after release from 10D of UUO (0.26 +/- 0.04) was lower than that of 10D of UUO (p<0.05) and much lower than those with 20D of UUO (p<0.001). However, rats treated with E from the time of UUO release had lower Vv(I/C) (0.21 +/- 0.07) than UUO released E untreated rats (p<0.05). Release of UUO initiates regression of interstitial expansion in rats. ACEI with enalapril significantly accelerates reversal of interstitial expansion after UUO release. This could have important implications for treatment of obstructive nephropathy in humans.
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PMID:Enalapril accelerates remodeling of the renal interstitium after release of unilateral ureteral obstruction in rats. 1277 69

The objective of this paper was to evaluate potential beneficial effects of combined treatment with slow-release nitrates and angiotensin converting enzyme inhibitors (ACE) on left ventricular remodeling and exercise capacity in patients after acute myocardial infarction. In this study, 141 patients (aged 34 to 74, mean 56.6 years) with sufficient circulation received combined treatment with 24 hour nitroglycerin infusion followed by oral nitrates (isosorbide mononitrate 50 mg OD) from day 2 day 42 after myocardial infarction and ACE inhibitor (captopril 25 mg BID or enalapril 5 mg BID versus placebo) from day 10 to day 42. On days 10 and 42, echocardiographic examination was carried out and recorded on an optical disc. Simultaneously, on the same days, the treadmill exercise test (modified Bruce protocol) was performed. In the echocardiographic study the left ventricular endodiastolic and endosystolic volumes (biplane Simpson formula), ejection fraction, left ventricular wall motion score and left ventricular mass index were analyzed. Treadmill test criteria, used in the study, included exercise duration time and workload (METS). For each patient the data obtained examination II and I were measured and the differences in their values were classified. The obtained results were analyzed with one-way and three-way ANOVA test. A Kruskal-Wallis test was also used in one variable analysis. Results were analyzed after repartition of patients into groups according type of treatment (angiotensin converting ing enzyme inhibitor or placebo), infarct location (anterior or inferior wall) and enzyme level (CPK < 2000 IU/L or CPK > 2000 IU/L). A p value < 0.1 was considered statistically significant. In a single factor analysis ANOVA proved that the patients treated with nitrates and captopril showed greater improvement in exercise capacity (in METS) than patients treated with enalapril or placebo (+1.26 captopril, +0.2 enalapril and +0.29 placebo, p = 0.043). In addition, a decrease in left ventricular mass index was evident only in patients treated with angiotensin converting enzyme inhibitor (placebo +7.37 gm/m2, captopril -12.17 gm/m2, enalapril -10.14 gm/m2, p = 0.0032). The triple factor analysis ANOVA test revealed that the change in endodiastolic left ventricular volume depends on combination of three factors: infarct location, type of treatment and level of cardiac enzymes (p = 0.009). A decrease in left ventricular endodiastolic volume between day 42 and 10 was observed only in patients with inferior wall infarct and CPK level < 2000 IU/L, irrespective of treatment type and in patients with inferior wall infarct and CPK level > 2000 IU/L treated with angiotensin enzyme inhibitor. We noticed also that heart failure, considered as contraindication to randomization, was in addition the most frequent (up to day 10) cause for study termination and initiation of treatment with angiotensin enzyme inhibitor.
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PMID:[The impact of nitrates and mono-therapy and nitrates combined with angiotensin converting enzyme inhibitors on left ventricular remodeling and exercise capacity in patients after acute myocardial infarction]. 1293 52

The association of the ACE gene I/D polymorphism with type 2 diabetes (DM) was examined in a population-based Japanese sample. A total of 902 individuals (490 females and 412 males, age 58.8 +/- 12.2 yr) from a cohort population (n = 3,706) of the Funagata diabetes study were divided into three groups according to genotype: D/D (n = 104), I/D (n = 436) and I/I (n = 362). Chi-square test and ANOVA were used for association studies and to assess the differences in the traits' values, respectively. More individuals with the genotypes D/D and I/D were diabetic (8.7% and 4.1%, respectively) than those with the genotype I/I (2.8%, p = 0.008 and p = 0.032, respectively). The genotype D/D was a risk factor for DM (relative risk (RR) 3.13, 95% CI 1.31-7.51), and also for DM and IGT (RR 1.78, 95% CI 14-2.76). Multiple logistic regression analysis also showed that the genotypes with the D allele were risk factors for DM and IGT even when adjusting for age, sex, hypertension and serum total cholesterol levels (odds ratio 1.49, 95% CI 1.01-2.21). The D allele of the ACE gene I/D polymorphism is a risk factor for DM.
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PMID:The D allele of the angiotensin-converting enzyme insertion/ deletion (I/D) polymorphism is a risk factor for type 2 diabetes in a population-based Japanese sample. 1459 12

Genetic variation in the human angiotensin I-converting enzyme (ACE) gene has been associated with many heritable traits, including obesity. Herein, we report the results of a study of obesity-related phenotypes and lifestyle in 1016 teen-aged Greeks. We show that there is a strong association (p = 0.001) between subcutaneous fat and the ACE insertion/deletion (I/D) polymorphism in females, possession of genotypes containing the D allele being associated with increased fat thickness. This association is strongest in females who participate in no extra exercise and accounts for 6.5% of the phenotypic variance in fat thickness by ANOVA. The association is additive, with the mean phenotypic values in heterozygotes intermediate between the means of the two homozygotes, and the association acts at both extremes of the fat thickness distribution in a classical polygenic manner. Other ACE polymorphisms (rs4424958, rs4311) that define major haplotypes in European populations fail to provide stronger associations with the subcutaneous fat phenotype. Because ACE I/D is the polymorphism most strongly associated with circulating ACE levels in European populations, we propose that the functional allelic differences that influence circulating ACE levels also mediate the associations with the obesity-related phenotypes studied here.
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PMID:Effects of interaction between angiotensin I-converting enzyme polymorphisms and lifestyle on adiposity in adolescent Greeks. 1622 48

Limited evidence suggests renin-angiotensin-aldosterone system (RAAS) polymorphisms alter the blood pressure (BP) response to aerobic exercise training. We examined if RAAS polymorphisms influenced postexercise hypotension in men with high normal to Stage 1 hypertension. Forty-seven men (44.2+/-1.4 years, 145.1+/-1.6/85.5+/-1.1 mmHg) randomly completed three experiments: seated rest (control) and two cycle exercise bouts at 40% (LITE) and 60% (MOD) of maximal oxygen consumption. Ambulating BP was measured for 14 h after each experiment. RAAS polymorphisms associated with hypertension (i.e. angiotensin converting I enzyme, ACE I/D; angiotensin II type 1 receptor, AT1R A/C; and intron 2 of aldosterone synthase, Int2 W/C) were analyzed using polymerase chain reaction and restriction enzyme digestion. Repeated measure ANOVA tested if BP differed between experimental conditions by RAAS genotypes. Compared to men with 0-2 variant alleles, men with > or =3 combined RAAS variant alleles had lower average systolic BP (SBP) (P=0.030) and lower average diastolic BP (DBP) (P=0.009) for 14 h only after LITE. In contrast, average BP was not different for MOD and control between RAAS variant allele groups over this time period (P> or =0.05). LITE reduced BP in men with > or =3 variant RAAS alleles for 14 h, whereas MOD had no influence on BP in these men. In order to optimally prescribe exercise for its BP lowering benefits in those with hypertension, additional knowledge of how genetic variation affects the BP response to exercise is needed.
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PMID:RAAS polymorphisms alter the acute blood pressure response to aerobic exercise among men with hypertension. 1646 60

Tissue factor (TF) plays a pivotal role in thrombus formation. Statins and angiotensin converting enzyme inhibitors attenuate expression of TF by distinct mechanism. Therefore, we hypothesized that combined therapy with simvastatin and ramipril may have additive beneficial anti-atherogenic effects to lower TF activity when compared with either drug alone. This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each treatment period. Simvastatin and ramipril monotherapy tended to reduce TF activity (0.53 to 0.46 nM, P=0.056; 0.54 to 0.50 nM, P=0.167, respectively) while combined therapy had a significant effect (0.64 to 0.43 nM, P<0.001). All three therapies significantly reduced prothrombin fragment 1+2 (F1+2) levels from their respective baselines (P=0.037, P<0.001, and P=0.057, respectively). Combined therapy significantly reduced TF activity and F1+2 levels to a greater extent than either simvastatin or ramipril alone (P=0.029 and P=0.040 by ANOVA, respectively). Percent changes in TF activity and percent changes in F1+2 levels were significantly correlated. All three therapies reduced CD40 ligand levels from their respective baselines (P=0.098, P<0.001, and P=0.002, respectively) with no significant differences among these three therapies (P=0.204 by ANOVA). Ramipril combined with simvastatin significantly reduces plasma TF activity and F1+2 levels to a greater extent than monotherapy with either drug in patients with type 2 diabetes.
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PMID:Combined therapy with ramipril and simvastatin has beneficial additive effects on tissue factor activity and prothrombin fragment 1+2 in patients with type 2 diabetes. 1696 76

The strong association between the angiotensin I-converting enzyme (ACE) gene I/D polymorphism with serum ACE activity appears lacking in Nigerians and Kenyans, but has not previously been well assessed in others of African origin. This study addressed this issue in an ethnically well defined black South African population. A putative association for the A22982G ACE gene variant, a QTL likely to impact on serum ACE activity, was also sought. Subjects were 200 healthy male black South African volunteers from the Xhosa ethnic group. Venous blood was obtained from all subjects for DNA extraction. ACE I/D and A22982G genotypes were determined and serum ACE activity measured. Age and blood pressure were recorded. For the group as a whole (mean +/- SD age 38.5 +/- 9.8 years, SBP 119.6 +/- 14.1 mmHg, DBP 78.2 +/- 10.1 mmHg) serum ACE activity was 38.2 +/- 11.2 nmol ml(-1)min(-1). ACE I/D genotype was not significantly associated with serum ACE activity. In contrast, the A22982G variant was significantly associated with serum ACE activity, being 35.9 +/- 9.6, 38.1 +/- 10.6 and 42.4 +/- 15.3 nmol ml(-1)min(-1) for AA, AG and GG genotypes respectively; p = 0.03 by ANOVA and p = 0.01 by linear trend. In keeping with the findings in some other African populations, the ACE I/D polymorphism is not strongly associated with serum ACE activity in Xhosa South Africans. As such, it cannot be used as a marker of ACE activity in these subjects. In this regard the use of the A22982G gene variant may be more appropriate.
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PMID:The impact of ACE genotype on serum ACE activity in a black South African male population. 1722 72

Unaccustomed exercise may cause muscle breakdown with marked increase in serum creatine kinase (CK) activity. The skeletal muscle renin-angiotensin system (RAS) plays an important role in exercise metabolism and tissue injury. A functional insertion (I)/deletion (D) polymorphism in the angiotensin I-converting enzyme (ACE) gene (rs4646994) has been associated with ACE activity. We hypothesized that ACE ID genotype may contribute to the wide variability in individuals' CK response to a given exercise. Young individuals performed maximal eccentric contractions of the elbow flexor muscles. Pre- and postexercise CK activity was determined. ACE genotype was significantly associated with postexercise CK increase and peak CK activity. Individuals harboring one or more of the I allele had a greater increase and higher peak CK values than individuals with the DD genotype. This response was dose-dependent (mean +/- SE U/L: II, 8,882 +/- 2,362; ID, 4,454 +/- 1,105; DD, 2,937 +/- 753, ANOVA, P = 0.02; P = 0.009 for linear trend). Multivariate stepwise regression analysis, which included age, sex, body mass index, and genotype subtypes, revealed that ACE genotype was the most powerful independent determinant of peak CK activity (adjusted odds ratio 1.3, 95% confidence interval 1.03-1.64, P = 0.02). In conclusion, we indicate a positive association of the ACE ID genotype with CK response to strenuous exercise. We suggest that the II genotype imposes increased risk for developing muscle damage, whereas the DD genotype may have protective effects. These findings support the role of local RAS in the regulation of exertional muscle injury.
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PMID:ACE ID genotype affects blood creatine kinase response to eccentric exercise. 1788 20

The proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1), act in concert to balance thrombus formation and degradation, thereby modulating the development of arterial thrombosis and excessive bleeding. PAI-1 is upregulated by the renin-angiotensin system (RAS), specifically by angiotensin II, the product of angiotensin converting enzyme (ACE) cleavage of angiotensin I, which is produced by the cleavage of angiotensinogen (AGT) by renin (REN). ACE indirectly stimulates the release of t-PA which, in turn, activates the corresponding fibrinolytic system. Single polymorphisms in these pathways have been shown to significantly impact plasma levels of t-PA and PAI-1 differently in Ghanaian males and females. Here we explore the involvement of epistatic interactions between the same polymorphisms in central genes of the RAS and fibrinolytic systems on plasma t-PA and PAI-1 levels within the same population (n = 992). Statistical modeling of pairwise interactions was done using two-way ANOVA between polymorphisms in the ETNK2, RENIN, ACE, PAI-1, t-PA, and AGT genes. The most significant interactions that associated with t-PA levels were between the ETNK2 A6135G and the REN T9435C polymorphisms in females (p = 0.006) and the REN T9435C and the TPA I/D polymorphisms (p = 0.005) in males. The most significant interactions for PAI-1 levels were with REN T9435C and the TPA I/D polymorphisms (p = 0.001) in females, and the association of REN G6567T with the TPA I/D polymorphisms (p = 0.032) in males. Our results provide evidence for multiple genetic effects that may not be detected using single SNP analysis. Because t-PA and PAI-1 have been implicated in cardiovascular disease these results support the idea that the genetic architecture of cardiovascular disease is complex. Therefore, it is necessary to consider the relationship between interacting polymorphisms of pathway specific genes that predict t-PA and PAI-1 levels.
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PMID:Epistatic interactions in genetic regulation of t-PA and PAI-1 levels in a Ghanaian population. 2130 99

In this study, the lateral geniculate bodies (LGB) of rats, bats and pangolins were compared using histological and quantitative histochemical parameters to observe possible modifications that enable these mammals to cope with their habitation particularly with respect to their diet. The study was conducted using ten adult Wistar rats, ten fruit bats and eight pangolins comprising of both sexes. After being sacrificed by cervical dislocation, their skulls were opened using bone forceps to expose the brains. The lateral geniculate bodies were excised from each brain tissue, homogenized and homogenate studied spectrophotometrically for the activities of lactate dehydrogenase (LDH), glucose-6-phosphate dehydrogenase (G-6-PDH), acid phosphatase (ACP), alkaline phosphatase (ALP) and acetylcholinesterase (AChE). The LGB tissue samples meant for histological studies were fixed in 10% formol calcium and processed for paraffin wax embedding. Serial sections of 3?m thickness were stained with Hematoxylin and Eosin (H &amp; E) and Cresyl fast violet (CFV) stains. The stained tissues were studied under the light microscope. Application of one-way ANOVA statistical method showed that there were significant differences (p&lt;0.05) in the activities of LDH, G-6-PDH, ACP, ALP and AChE of the LGB of the three mammals as revealed in the quantitative histochemistry of these enzymes and markers. Histological observations revealed no observable differences in the relative distribution of neurons and their supporting glial cells within the LGB of the three mammalian species. The comparison of the differences observed in the histological and the quantitative histochemical activities in these mammalian species revealed a variation in the visual perception and their individual peculiarities in relation to their mode and pattern of living.
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PMID:A comparative study of the lateral geniculate body of rat (Rattus norvegicus), bat (Eidolon helvum) and pangolin (Manis tricuspis). 2298 Mar 48


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