69,804 research outputs found
A genome-wide search replicates evidence of a quantitative trait locus for circulating angiotensisn l-converting enzyme (ACE) unlinked to the ACE gene
No full textBackground: angiotensin I-converting enzyme (ACE) plays an important role in cardiovascular homeostasis. There is evidence from different ethnic groups that circulating ACE levels are influenced by a quantitative trait locus (QTL) at the ACE gene on chromosome 17. The finding of significant residual familial correlations in different ethnic groups, after accounting for this QTL, and the finding of support for linkage to a locus on chromosome 4 in Mexican-American families strongly suggest that there may well be QTLs for ACE unlinked to the ACE gene.Methods: a genome-wide panel of microsatellite markers, and a panel of biallelic polymorphisms in the ACE gene were typed in Nigerian families. Single locus models with fixed parameters were used to test for linkage to circulating ACE with and without adjustment for the effects of the ACE gene polymorphisms.Results: strong evidence was found for D17S2193 (Zmax = 3.5); other nearby markers on chromosome 17 also showed modest support. After adjustment for the effects of the ACE gene locus, evidence of "suggestive linkage" to circulating ACE was found for D4S1629 (Zmax = 2.2); this marker is very close to a locus previously shown to be linked to circulating ACE levels in Mexican-American families.Conclusion: in this report we have provided further support for the notion that there are QTLs for ACE unlinked to the ACE gene; our findings for chromosome 4, which appear to replicate the findings of a previous independent study, should be considered strong grounds for a more detailed examination of this region in the search for genes/variants which influence ACE levels.
The poor yields, thus far, in defining the genetic determinants of hypertension risk suggest a need to look beyond simple relationships between genotypes and the ultimate phenotype. In addition to incorporating information on important environmental exposures, a better understanding of the factors which influence the building blocks of the blood pressure homeostatic network is also required. Detailed studies of the genetic determinants of ACE, an important component of the renin-angiotensin system, have the potential to contribute to this strategic objectiv
The UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factors
No full textThe UN-SUSTAINABLE Match in HCV Recipients. Evidences from the Italian D-MELD Study on Balancing Donor-Recipient Risk Factor
Do ACE inhibitors improve the response to exercise training in functionally impaired older adults? A randomized controlled trial
No full text<br>Background: Loss of muscle mass and strength with ageing is a major cause for falls, disability, and morbidity in older people. Previous studies have found that angiotensin-converting enzyme inhibitors (ACEi) may improve physical function in older people. It is unclear whether ACEi provide additional benefit when added to a standard exercise training program. We examined the effects of ACEi therapy on physical function in older people undergoing exercise training.</br>
<b>Methods:</b> Community-dwelling people aged ≥65 years with functional impairment were recruited through general (family) practices. All participants received progressive exercise training. Participants were randomized to receive either 4 mg perindopril or matching placebo daily for 20 weeks. The primary outcome was between-group change in 6-minute walk distance from baseline to 20 weeks. Secondary outcomes included changes in Short Physical Performance Battery, handgrip and quadriceps strength, self-reported quality of life using the EQ-5D, and functional impairment measured using the Functional Limitations Profile.<p></p>
<b>Results:</b> A total of 170 participants (n = 86 perindopril, n = 84 placebo) were randomized. Mean age was 75.7 (standard deviation [SD] 6.8) years. Baseline 6-minute walk distance was 306 m (SD 99). Both groups increased their walk distance (by 29.6 m perindopril, 36.4 m placebo group) at 20 weeks, but there was no statistically significant treatment effect between groups (−8.6m [95% confidence interval: −30.1, 12.9], p = .43). No statistically significant treatment effects were observed between groups for the secondary outcomes. Adverse events leading to withdrawal were few (n = 0 perindopril, n = 4 placebo).<p></p>
<b>Interpretation:</b> ACE inhibitors did not enhance the effect of exercise training on physical function in functionally impaired older people.<p></p>
The angiotensin-converting enzyme (ACE) gene family of Anopheles gambiae
No full textBackground
Members of the M2 family of peptidases, related to mammalian angiotensin converting enzyme (ACE), play important roles in regulating a number of physiological processes. As more invertebrate genomes are sequenced, there is increasing evidence of a variety of M2 peptidase genes, even within a single species. The function of these ACE-like proteins is largely unknown. Sequencing of the A. gambiae genome has revealed a number of ACE-like genes but probable errors in the Ensembl annotation have left the number of ACE-like genes, and their structure, unclear.
Results
TBLASTN and sequence analysis of cDNAs revealed that the A. gambiae genome contains nine genes (AnoACE genes) which code for proteins with similarity to mammalian ACE. Eight of these genes code for putative single domain enzymes similar to other insect ACEs described so far. AnoACE9, however, has several features in common with mammalian somatic ACE such as a two domain structure and a hydrophobic C terminus. Four of the AnoACE genes (2, 3, 7 and 9) were shown to be expressed at a variety of developmental stages. Expression of AnoACE3, AnoACE7 and AnoACE9 is induced by a blood meal, with AnoACE7 showing the largest (approximately 10-fold) induction.
Conclusion
Genes coding for two-domain ACEs have arisen several times during the course of evolution suggesting a common selective advantage to having an ACE with two active-sites in tandem in a single protein. AnoACE7 belongs to a sub-group of insect ACEs which are likely to be membrane-bound and which have an unusual, conserved gene structure
Angiotensin-converting enzyme I/D polymorphism and preeclampsia risk: Evidence of small-study bias
No full textBackground Inappropriate activation of the renin-angiotensin system may play a part in the development of preeclampsia. An insertion/deletion polymorphism within the angiotensin-I converting enzyme gene (ACE-I/D) has shown to be reliably associated with differences in angiotensin-converting enzyme (ACE) activity. However, previous studies of the ACE-I/D variant and preeclampsia have been individually underpowered to detect plausible genotypic risks.Methods and Findings A prospective case-control study was conducted in 1,711 unrelated young pregnant women (665 preeclamptic and 1,046 healthy pregnant controls) recruited from five Colombian cities. Maternal blood was obtained to genotype for the ACE-I/D polymorphism. Crude and adjusted odds ratio (OR) and 95% confidence interval (CI) using logistic regression models were obtained to evaluate the strength of the association between ACE-I/D variant and preeclampsia risk. A meta-analysis was then undertaken of all published studies to February 2006 evaluating the ACE-I/D variant in preeclampsia. An additive model (per-D-allele) revealed a null association between the ACE-I/D variant and preeclampsia risk (crude OR 0.95 [ 95% Cl, 0.81-1.10]) in the new case-control study. Similar results were obtained after adjusting for confounders (adjusted per-allele OR 0.90 [ 95% CI, 0.77-1.06]) and using other genetic models of inheritance. A metaanalysis (2,596 cases and 3,828 controls from 22 studies) showed a per-allele OR of 1.26 (95% CI, 1.07-1.49). An analysis stratified by study size showed an attenuated OR toward the null as study size increased.Conclusions It is highly likely that the observed small nominal increase in risk of preeclampsia associated with the ACE D-allele is due to small-study bias, similar to that observed in cardiovascular disease. Reliable assessment of the origins of preeclampsia using a genetic approach may require the establishment of a collaborating consortium to generate a dataset of adequate size
Incidence of childhood-onset insulin-dependent diabetes mellitus: the Eurodiab ACE study
No full textAngiotensin-converting enzyme insertion/deletion polymorphism does not influence the restenosis rate after coronary stent implantation
No full textBackground. Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. Methods: As a substudy of the optimization with intracoronary, ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography tinder identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. Results: With respect to the ACE gene polymorphism, there were three subgroups: DID genotype (48 patients), ID (83 patients) and 11 (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853-5.493). We obtained the following results for ACE serum levels: 0.53 mumol/l/s in the DD subgroup, 0.29 mumol/l/s in the ID
Angiotensin converting enzyme and vascular endothelial growth factor responses to exercise training in claudicants: the role of ace inhibition
No full textExercise training is well recognised as an effective treatment for intermittent claudication. The mechanism underlying exercise induced improvements is multi-factorial but remains poorly understood. Low angiotensin-converting enzyme (ACE) activity has been associated with enhanced responses to endurance training. Specifically, low ACE activity has been associated with improved muscle metabolism, endothelial function, and suppressed inflammatory responses; processes linked with exercise training benefits in claudicants. Furthermore, pharmacological inhibition of ACE has been associated with enhanced angiogenesis in animal models of ischaemia, secondary to increases in vascular endothelial growth factor (VEGF). In this study, 11 claudicants were randomised to 8 weeks of supervised exercise training (n=6) or exercise advice (n=5). Walking ability was recorded before and after this period, and blood samples taken. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the effects of exercise training on ACE, VEGF and VEGF receptor (VEGFR) gene expression, and enzyme-linked immunosorbant assays (ELISA) measured changes in ACE and VEGF protein levels. In another experiment, a cell culture model of hypoxia, utilising ECV 304 cells and diethylenetriamine-nitric oxide (DETA-NO), was used to study the effects of the ACE inhibitor ramiprilat on ACE and VEGF responses to hypoxia, using RT-PCR and ELISA.
Supervised exercise improved claudication distance by 105 metres (p < 0.05) and maximum walking distance by 141 metres (p < 0.05). ACE mRNA expression increased 30%, VEGF121 expression 43% and VEGF165 expression 70% (all p < 0.05). Soluble VEGFR-1 mRNA expression increased by 63% and VEGFR-2 72% (both p < 0.05). ACE and VEGF protein levels remained comparatively stable. In the cell culture experiments, ramiprilat increased VEGF protein levels in hypoxia. Although a lack of experimental runs prevented statistical analysis, the results also suggest that ramiprilat has a stimulatory effect on ACE mRNA expression in hypoxia.
Improvements in walking ability after exercise training are associated with increases in both VEGF and VEGF receptor expression. ACE inhibitors could play a role in improving claudication by potentiating increases in VEGF in addition to their known action of suppressing ACE activity
Observation of sulphate aerosols and SO2 from volcanic eruptions using data from the Atmospheric Chemistry Experiment (ACE)
No full textInfrared spectra measured by the Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) on board of the SCISAT satellite were used to analyse the temporal and spatial evolution of volcanic aerosols
from the Kasatochi (August 2008), Sarychev (June 2009) and Grimsvötn (May 2011) eruptions. Evidence of the Kasatochi and Sarychev eruptions has first be seen one month after the eruptions, while the Grimsvötn plume has been detected with a maximum age of 3 days, from enhanced SO2 concentrations and atmospheric extinction. Evidence for differences within these plumes have been obtained, showing the evolution of H2 SO4 from no sulphate aerosol signature in fresh volcanic plumes to clear signatures in aged volcanic plumes. The atmosphere had returned to pre-eruption conditions, between seven and eight months after the eruptions of Kasatochi and Sarychev.
The first SO2 and sulphate aerosol retrievals determined using the infrared solar occultation spectra recorded with ACE-FTS are presented here. The size distribution parameters, aerosol volume slant column and composition of the sulphate aerosol were obtained using a least-squares algorithm, employing a continuum spectrum between 800 − 4200 cm−1 . The maximum volume slant column of the aerosol was found to be 500 μm3 cm−3 km (for Kasatochi) and 850 μm3 cm−3 km (for Sarychev), which results in an approximate aerosol loading of 1.8 μm3 cm−3 and 3 μm3 cm−3, respectively. One month after the eruptions the effective radius (Reff ) is below 0.2 μm (Kasatochi) and 0.1 − 0.3 μm (Sarychev)
Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers.
No full textAmyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer's disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8074; replication n = 5042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for Aβ42 and BIN1 for pTau. GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume
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