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)

Preventing the progression of established heart failure can be difficult, as multiple factors contribute to the continual decline of cardiac function. Blunting the activated neurohormonal response to a decreased systolic function is a proven means of slowing progression of CHF. Preventing further CAD and cardiac ischemia may also prove to be an effective mechanism. Two trials with HMGCoA reductase inhibitors lend support to this hypothesis. Studies using ACE inhibitors may also support this notion. Since a major portion of heart failure in the USA is caused by CAD, preventing CHF progression may be related to the prevention of CAD. Using ACE inhibitors and lipid-lowering agents, in addition to standard measures of CAD risk factor modification, may prove useful in future trials to retard the progression of heart failure. Further research and clinical trials involving this method of CHF prevention are warranted.
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PMID:Role of secondary prevention in congestive heart failure due to coronary artery disease. 989 17

The sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion which is known as plaque rupture is the potential mechanism for the development of acute coronary syndrome (ACS). Accordingly, secondary prevention of ACS could be achieved with the prevention of the plaque rupture and thrombus formation. Coronary angioplasty and coronary bypass surgery have a limited value in the long-term prevention of ACS. Coronary risk factor modification is certainly the important strategy for secondary prevention. The drug treatment with lipid lowering agents, especially 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase inhibitors, beta-adrenergic receptor blockers, antiplatelet agents and anticoagulants, have been proven to be effective for the secondary prevention of myocardial infarction. Estrogen for postmenopausal women has also been reported to be beneficial. However, calcium channel blockers except verapamil, nitrates and angiotensin converting enzyme (ACE) inhibitors are not recommended for the secondary prevention of ACS.
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PMID:[Secondary prevention of acute coronary syndrome]. 1034 35

Do extremely old persons have a genetically favourable profile which has protected them from cardiovascular death? We have tried to answer this question by measuring DNA polymorphisms of selected cardiovascular risk indicators [factor VII, FVII (R/Q353, intron 7 (37bp)n, and -323ins10), beta fibrinogen (-455G/A), plasminogen activator inhibitor type 1, PAI-1 (-675(4G/5G)), tissue plasminogen activator, t-PA (intron 8 ins311), platelet receptor glycoprotein IIb/IIIa, GPIIb/IIIa (L/P33), prothrombin (20210G/A), methylene tetrahydrofolate reductase, MTHFR (A/V114), angiotensin converting enzyme, ACE (intron 16 ins287), and angiotensinogen (M/T235)]. Blood was collected from 187 unselected Danish centenarians, and 201 healthy Danish blood donors, aged 20-64 years (mean age 42 years). Genomic DNA was amplified using PCR and the genotype was determined by RFLP methods or allele-specific amplification followed by agarose gel electrophoresis. The frequencies of the high-risk alleles in centenarians were: for FVII R/Q353 0.91; for FVII intron 7 (37bp)n 0.67; for FVII-323 ins10 0.90; for fibrinogen 0.16; for PAI-1 0.52; for t-PA 0.59; for GPIIb/IIIa 0.16; for prothrombin 0.008; for MTHFR 0.33; for ACE 0.52; and for angiotensinogen 0.36. Comparable frequencies were observed in the blood donors. Subgroup analysis of men and women separately gave similar results. The genotype frequencies in the centenarians and the blood donors were similar for all polymorphisms, and this study suggests that common variations in genes associated with cardiovascular risk do not contribute significantly to longevity.
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PMID:Longevity is independent of common variations in genes associated with cardiovascular risk. 1049 71

Angiotensin II (Ang II) was shown to be an important risk factor for accelerated atherosclerosis. Inhibition of Ang II action on the arterial wall by blocking its production with angiotensin converting enzyme (ACE) inhibitors, or by blocking binding to its receptors on cells with antagonists was shown to attenuate atherogenesis in animal model of atherosclerosis. We questioned whether Ang II atherogenicity is related to a stimulatory effect of Ang II on macrophage cholesterol biosynthesis. Angiotensin II injected intraperitoneally once a day (0.1 ml of 10(-7) M per mouse) for a period of 30 days, to the apolipoprotein E deficient mice increased the atherosclerotic lesion area by 95% (P < 0.01 vs. control), compared to placebo-injected mice, with no significant effect on blood pressure or on plasma cholesterol levels. On using mouse peritoneal macrophages (MPMs) that were harvested after intraperitoneally injection of Ang II, an increased rate of cellular cholesterol biosynthesis (measured as incorporation of [3H]acetate into cholesterol) by up to 90% (P < 0.01 vs. control) was observed. In mice treated with the ACE inhibitor, Fosinopril (25 mg/kg per day) a reduction in their MPM's cholesterol synthesis by up to 70% (P < 0.01 vs. control) was obtained. In vitro studies in human monocyte-derived macrophages (HMDM), in MPMs from control BALB/c mice, and in J-774 A.1 macrophage-like cell line demonstrated up to 44, 34 and 30% stimulation of macrophage cholesterol biosynthesis, respectively, following cell incubation with 10(-7) M Ang II for 18 h at 37 degrees C. The stimulatory effect of Ang II on macrophage cholesterol biosynthesis could be related to its interaction with the macrophage AT1 receptor, as Losartan (10(-5) M), an AT1 blocker, but not PD 123319 (10(-5) M), an AT2 blocker, prevented the stimulatory effect on macrophage cholesterol synthesis. Furthermore, in cells that lack the AT1 receptor (RAW macrophages), Ang II did not increase cellular cholesterol synthesis. Ang II increased macrophage 3-hydroxy-3-methyl glutaryl CoA (HMG CoA) reductase mRNA levels in a dose dependent manner in J-774 A.1 macrophages and in MPM. Losartan, the AT1 receptor antagonist clearly attenuated this mRNA induction. We thus conclude that Ang II stimulation of macrophage cholesterol biosynthesis is related to its interaction with the AT1 receptor, followed by stimulation of macrophage HMG CoA reductase gene expression, which leads to increased cellular cholesterol biosynthesis, and can possibly result in macrophage cholesterol accumulation and foam cell formation.
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PMID:Angiotensin II atherogenicity in apolipoprotein E deficient mice is associated with increased cellular cholesterol biosynthesis. 1053 81

Allograft coronary endothelial cells can serve as potent stimulators (antigen-presenting cells) as well as targets of allogeneic lymphocyte reactivity. Independent of the cause leading to endothelial cell injury after transplantation, endothelial cell activation and dysfunction occurs, associated with modification in endothelial cell-dependent molecule expression. The prevalence of coronary endothelial vasomotor dysfunction is approximately 20-30% during the first year, and 30-40% in the long-term follow-up. Importantly, no association is detectable between endothelial dysfunction and intimal thickness, suggesting two distinct entities of allograft vasculopathy. Early predictors of vasomotor dysfunction are proinflammatory cytokines and endothelin expression. Repetitive subendocardial ischemia during myocardial stress (due to microvascular dysfunction) may result in an impairment of left ventricular function. In non-transplant patients coronary endothelial dysfunction predicts cardiac events during long-term follow-up. It is reasonable that early administration of endothelial-protective compounds is necessary for protection of allograft endothelial dysfunction and vasculopathy during follow-up. The explanted donor heart may offer a potential for gene therapy techniques including modification of allograft phenotype and modulation of the host alloimmune response. Other protective strategies may include improvement of cardioplegic solutions and reperfusion strategies, recovery of the imbalance between vasoactive mediators, and treatment with HMG-CoA-reductase inhibitors and/or ACE inhibitors.
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PMID:Heart allograft endothelial cell dysfunction. Cause, course, and consequences. 1115 95

In cardiovascular pharmacotherapy, the main focus is now on statins (HMG-CoA-reductase inhibitors) because of their antihyperlipidaemic and antiatherogenic effect. They are suggested to be beneficial also in senile dementia, stroke and osteoporosis and they can reduce incidence of ventricular arrhythmias in patients with cardioverter-defibrillator. In chronic heart failure, statins should be used with caution since reduced cholesterol levels relate to impaired survival. As an alternative to statins and fibrates, niacin therapy may be considered. ACE inhibitors are of proven benefit for patients with left ventricular dysfunction after acute myocardial infarction; however, in long-term treatment, their protective activity is not superior to that of beta-blockers, diuretics and clonidine. Ca-channel antagonists slightly increase the incidence of cardiovascular complications but reduce the incidence of stroke in high-risk patients. Biventricular pacing has been used with success in patients with severe heart failure and conduction disturbances, and the first permanent artificial ventricle was implanted to a patient with irreversible terminal heart failure in summer 2000. Cardiospecific troponin I may be an uninvasive marker of a procoagulant status indicating e.g. graft failure after cardiac transplantation; T-cadherin belongs to the cell-adhesion molecules and has a role in maintenance of cellular contacts which are critical for the vessel wall architecture. Etamoxir, originally developed for the treatment of diabetes II, has recently been shown to be a potential novel drug for heart failure. Routine use of nitric oxide after congenital heart surgery lessens the risk of pulmonary hypertensive crises.
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PMID:[Cardiology 2000]. 1137 23

We carried out an association (case-control) study of five candidate genes--G-protein beta3 subunit gene variant; methylene tetrahydrofolate reductase (MTHFR); angiotensin converting enzyme (ACE) gene; and paraoxonase 1 and 2 (PON 1 and 2) genes--in a United Arab Emirati population. The aim was to establish a possible relationship between these five candidate genes and clinical left ventricular hypertrophy (LVH) in a genetically homogenous group. DNA samples were collected from 213 unrelated Nationals who were further segregated into 98 subjects with LVH (78 hypertensives and 20 normotensives) and 115 (23 hypertensives and 92 normotensives) age- and sex-matched controls who did not present with LVH. Of the five candidate gene markers studied, no significant differences in the genotype distribution of the MTHFR, PON 1 and 2 or ACE markers were found between the LVH and non-LVH groups. However, a possible association was found between the beta3 G-protein C825T marker and LVH. In conclusion, our results suggest an association between LVH and the C825T allele of the G-protein beta3 subunit gene.
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PMID:An association study of five genetic loci and left ventricular hypertrophy amongst Gulf Arabs. 1176 21

We investigated the effects of a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, an angiotensin converting enzyme (ACE) inhibitor, temocaprilat, and an angiotensin II type 1 (AT1) receptor antagonist, CV-11974, on myocardial metabolism during ischemia in isolated rabbit hearts using phosphorus 31-nuclear magnetic resonance (31P-NMR) imaging. Forty-five minutes of continuous normothermic global ischemia was carried out. Pravastatin, temocaprilat, CV-11974 or a nitric oxide synthase inhibitor, L-NAME was administered from 60 min prior to the global ischemia. Japanese white rabbits were divided into the following experimental groups, a control group (n=7), a group treated with pravastatin (P group; n=7), a group treated with pravastatin and temocaprilat (P+T group; n=7), a group treated with pravastatin and CV-11974 (P+CV group; n=7), and a group treated with pravastatin and L-NAME (P+L-NAME group; n=7). During ischemia, P group, as well as either P+T group or P+CV group, showed a significant inhibition of the decreases in adenosine triphosphate (ATP) and intracellular pH (pHi) (p<0.01, respectively, at the end of ischemia compared to the control group as well as P+L-NAME group), and a significant inhibition of the increase in inorganic phosphate (Pi) (p<0.01, respectively, compared with the control group as well as P+L-NAME group). These results suggest that pravastatin significantly improved myocardial energy metabolism during myocardial ischemia. This beneficial effect was dependent on NO synthase. However, this beneficial effect was not enhanced by either temocaprilat or CV-11974.
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PMID:Effects of an HMG-CoA reductase inhibitor in combination with an ACE inhibitor or angiotensin II type 1 receptor antagonist on myocardial metabolism in ischemic rabbit hearts. 1204 36

A comparative study has been performed on populations of Unionidae from the Lake Suszek and Brda river situated in the centre of Tucholski Landscape Park, around which there are no factories and the Pilica river--affected by the influence of the nearby town agglomeration. Mussels collected from Suszek were also treated (72 h) with various concentrations of dichlorophenol (DCP; 0.1, 0.15, 0.2 ppm) and paraquat (PQ; 1, 5, 10 ppm) in laboratory conditions (aquarium). The activities of glutathione S-transferase (GST) and cytochrome P450 monooxygenase system (NAD(P)H ferricyanide reductase, NAD(P)H cytochrome c reductase), cytochrome P450 content and b(5) in microsomal and cytosolic fractions of digestive gland were investigated. The differences in enzyme activities between groups of mussels, which were exposed to various concentrations of chemical pollutants, as well as the dependence on geographical distribution in Poland, were observed. In experiments with DCP the dose-dependent increase in GST activity was found, but no changes after PQ treatment were observed. Results, in experiments with DCP and PQ, have varied from no change to increase or decrease in the measured monooxygenase activities and cytochrome P450 content. Increases have been recorded in two cases (NADPH ferricyanide reductase and cytochrome P450) after exposure to DCP and in the case of NADH ferricyanide reductase following the exposure to PQ. NAD(P)H cytochrome c reductase activity and content of P450 decreased considerably in 5 and 10 ppm PQ-treated mussels. Thus, the treatment with DCP and PQ in water changed the properties of the mussels digestive gland cytochrome P450 monooxygenase system. These changes may be used as a bioindicator, at the molecular level, of exposure to those xenobiotics not only in controlled experiments (aquaria) but also in the natural environment.
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PMID:Comparative study of the xenobiotic metabolising system in the digestive gland of the bivalve molluscs in different aquatic ecosystems and in aquaria experiments. 1229 71

Progress in clinical and basic research of Alzheimer's disease (AD) suggested theoretical models of possible pathogenetic mechanisms, with a primary role of the genetic factors that have been implicated in AD. These can be divided into two main categories. First, the three genes in which mutations are known to result in early onset autosomal dominant familial AD (presenilins 1 and 2, and amyloid beta protein precursor [APP]): well characterized but that account for only a small proportion of AD cases. Secondly, late onset, sporadic AD is more common and evidence suggests that there is a genetic component to this type of disease. A number of genetic risk factors have been implicated that might increase the risk of developing sporadic disease: particularly, apolipoprotein E (apo E) polymorphism and many others suggested by linkage studies [alpha-macroglobulin, low density receptor protein (LRP1), bleomycin hydrolase], with a precise role in beta-amyloid metabolism and deposition. Many of these are controversial and studies have shown conflicting results, but apoE polymorphism seems to be only one of the possible genetic factors suggested to play a role in the multifactoral pathogenesis of AD. Regional and ethnic differences may affect the strength of association between apoE epsilon 4 allele and the disease, and we reported evidences of the decreasing frequency of epsilon 4 allele in AD patients and centenarians from Northern to Southern European regions. Finally, several genetic risk factors of vascular origin (angiotensin converting enzyme, methyltetrahydropholate-reductase, and NOS3 gene polymorphisms) have been implicated in the development of both vascular dementia and AD with conflicting results.
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PMID:[Genetics of late-onset Alzheimer's disease: vascular risk and beta-amyloid metabolism]. 1235 88


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