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)

The purpose of the study was to evaluate the clinico-diagnostic importance of the degree of inflammation and endothelial dysfunction in patients with chronic heart failure (CHF) receiving either standard therapy including ACE inhibitors or the same therapy plus aspirin. One hundred twenty CHF patients aged 45 to 74 were examined. The patients were studied clinically; laboratory tests included measurement of the cerum levels of cytokines with solid-phase immune enzyme assay and serum C-reactive protein (CRP) levels with photometric turbidimetric technique; the vasoregulating function and antithrombogenic activity of vascular wall were evaluated. Improvement in the clinical condition of II to III functional class patients receiving standard therapy was associated with a decrease in pro-inflammatory cytokine and CRP serum levels, as well as a tendency towards improvement in the vasoregulating function and a decrease in the antithrombogenic endothelial activity, mostly due to vascular wall fibrinolytic activity. Standard therapy combined with aspirin led to less prominent changes in the patients' conditions; a simultaneous decrease in the levels of all the cytokines under study was not noted; the vasoregulating activity of the vascular endothelium decreased. The data obtained may be used as additional criteria to objectively evaluate the severity of the condition of CHF patients and to control the effectiveness of the therapy.
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PMID:[The degree of inflammation and endothelial dysfunction in treatment of chronic heart failure in patients with coronary artery disease]. 1729 77

Atherosclerosis is a chronic inflammatory process. The adhesion of leukocytes to the vascular endothelium, mediated by endothelial cell adhesion molecules including vascular adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), and E-selectin, is the pivotal early event in atherogenesis. Inflammatory cytokines could activate redox-sensitive transcription factors and induce endothelial expression of adhesion molecules, which could be inhibited to various degrees by different antioxidants suggesting the potential role of endogenous reactive oxygen species (ROS) in atherogenesis. Many clinical drugs that against cardiovascular diseases have exhibited antioxidant effects; these drugs simultaneously inhibit endothelial adhesion molecule expression, such as aspirin, probucol, HMG-CoA reductase inhibitors, angiotensin receptor blockers, angiotensin converting enzyme inhibitors, peroxisome proliferator-activated receptor alpha and gamma ligands, calcium channel blockers, beta-adrenergic blockers, etc. In addition, we have previously demonstrated that Ginkgo biloba extract, a Chinese herb with antioxidant activity, could significantly suppress inflammatory cytokine-stimulated endothelial adhesiveness to human monocytic cells by attenuating intracellular ROS formation, redox-senstive transcription factor activation, and VCAM-1 as well as ICAM-1 expression in human aortic endothelial cells. The similar anti-atherosclerosis effects have been also shown in other Chinese herbs or dietary supplements with antioxidant activity such as magnolol and salvianolic acid B either in vitro or in vivo. Thus, oxidative stress is critical to endothelial adhesiveness in atherogenesis. The inhibition of endothelial adhesion molecule expression by drugs/agents with antioxidant activity may serve as a potential therapeutic strategy for clinical atherosclerosis.
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PMID:Anti-inflammatory effects of different drugs/agents with antioxidant property on endothelial expression of adhesion molecules. 1737 73

A total of 58 patients with ischemic heart disease and angina of effort (FC II) (mean age 55.6 years) participating in the study were diagnosed to have erective dysfunction (ED) of a mild (35%), moderate (57%) and severe degree (8%). All the patients were randomized into two groups. Group 1 (n=21, mean age 56.4 years) received standard cardiotropic therapy (nitrates, beta-blockers, ACE inhibitors on demand, diuretics, antioxidants) and placebo. Group 2 (n=37, mean age 54.3 years) received the same standard cardiotropic therapy plus impase (1 tablet each other day for 3 months). The results of the trial show that impase addition to cardiotropic therapy raised exercise tolerance, diminished the number of anginal attacks in mild and moderate exercise, enhanced coronary microcirculatory blood flow, increased reserve circulation index by 34%, improved metabolism of vascular endothelium in the whole body. Impase acts pathogenetically in endothelial insufficiency. Prevention of endothelial dysfunction by impase allows both to stop progression of cardiovascular disease and to prevent erectile dysfunction.
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PMID:[Treatment of erectile dysfunction in patients with ischemic heart disease and angina of effort]. 1791 21

Diabetes mellitus is associated with an increased risk of cardiovascular disease, even in the presence of intensive glycemic control. Substantial clinical and experimental evidence suggest that both diabetes and insulin resistance cause a combination of endothelial dysfunctions, which may diminish the anti-atherogenic role of the vascular endothelium. Both insulin resistance and endothelial dysfunction appear to precede the development of overt hyperglycemia in patients with type 2 diabetes. Therefore, in patients with diabetes or insulin resistance, endothelial dysfunction may be a critical early target for preventing atherosclerosis and cardiovascular disease. Microalbuminuria is now considered to be an atherosclerotic risk factor and predicts future cardiovascular disease risk in diabetic patients, in elderly patients, as well as in the general population. It has been implicated as an independent risk factor for cardiovascular disease and premature cardiovascular mortality for patients with type 1 and type 2 diabetes mellitus, as well as for patients with essential hypertension. A complete biochemical understanding of the mechanisms by which hyperglycemia causes vascular functional and structural changes associated with the diabetic milieu still eludes us. In recent years, the numerous biochemical and metabolic pathways postulated to have a causal role in the pathogenesis of diabetic vascular disease have been distilled into several unifying hypotheses. The role of chronic hyperglycemia in the development of diabetic microvascular complications and in neuropathy has been clearly established. However, the biochemical or cellular links between elevated blood glucose levels, and the vascular lesions remain incompletely understood. A number of trials have demonstrated that statins therapy as well as angiotensin converting enzyme inhibitors is associated with improvements in endothelial function in diabetes. Although antioxidants provide short-term improvement of endothelial function in humans, all studies of the effectiveness of preventive antioxidant therapy have been disappointing. Control of hyperglycemia thus remains the best way to improve endothelial function and to prevent atherosclerosis and other cardiovascular complications of diabetes. In the present review we provide the up to date details on this subject.
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PMID:Endothelial dysfunction in diabetes mellitus. 1820 Aug 6

Migraine is a common debilitating neurovascular disorder. The vascular genes ACE and MTHFR are involved in alterations in vascular endothelium and are suggested to play a role in migraine susceptibility. The aim of our study was to find out the role of ACE ID (rs no. 4646994) and MTHFR C677T (rs no.1801133) polymorphisms in genetic susceptibility of migraine in north Indian population. A total of 150 migraine patients, 220 non-migraine headache patients (Disease controls) and 150 age-sex matched normotensive healthy controls were enrolled for our study. DNA was isolated from peripheral blood leucocytes, and subjected to amplification using specific primers and genotyped using PCR (in case of ACE ID) or PCR-RFLP (in case of MTHFR C677T) methods. chi(2) test was applied for the analysis of genotypic and allelic distributions. Logistic regression analysis was used to find out contribution of genetic polymorphisms to the risk of disease. ACE DD genotype showed significant association in migraine patients with aura (MA) but a marginal significance in female MA patients in comparison with healthy controls. No significant differences in genotype and allelic frequencies of MTHFR C677T polymorphism were found on comparing migraine patients with either disease controls or healthy controls. In contrast, we found synergistic role of ACE (DD)*MTHFR (CT) interaction, showing a positive association in total migraine with aura patients as well as female migraine patients with aura when compared with healthy controls.
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PMID:Role of the ACE ID and MTHFR C677T polymorphisms in genetic susceptibility of migraine in a north Indian population. 1908 Nov 15

Oxidative stress is a key feature in vascular homeostasis. Reactive oxygen species (ROS) are produced by multiple enzymatic sources located in various anatomical structures of the vascular wall, such as the vascular endothelium, the smooth muscle cells and inflammatory cells infiltrating sub-endothelial space and the rest of the vascular wall. Although ROS behave as signaling molecules regulating important aspects of vascular physiology, their excess generation is harmful. Further to the cytotoxic effect of ROS in the vascular wall, they also activate various redox sensitive transcription pathways, regulating the expression of proinflammatory molecules with strong pro-atherogenic effects. The activation of redox-sensitive enzymatic systems in the vascular wall such as matrix metalloproteinases as well as the impairment of endothelial function have a significant impact on vascular elasticity and vascular mechanics in general. The impairment of vascular mechanics has a significant impact on vascular homeostasis, promoting atherogenesis. It is therefore crucial to regulate vascular redox signaling, by developing therapeutic strategies able to target the effectively intracellular ROS bioavailability. Statins, angiotensin converting enzyme inhibitors, thiazolidinediones, folates, tetrahydrobiopterin and other therapeutic strategies seem promising in targeting vascular redox signaling, although it is still unclear which of these treatments have the potential to effectively prevent atherogenesis. Future studies need to define the key redox sensitive pathways in the vascular wall in order to develop effective therapeutic strategies against atherosclerosis.
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PMID:Targeting redox signaling in the vascular wall: from basic science to clinical practice. 1914 22

Cardiovascular diseases (CVD) are the leading cause of mortality in Croatia and in Europe. Primary prevention of CVD involves intervention before the onset of disease, and prevention of modifiable risk factors, i.e. cigarette smoking, hyperlipidemia, arterial hypertension, diabetes mellitus, inactivity, obesity. These risk factors are strongly associated and lead to impaired vascular endothelial function, chronic injury of endothelium, platelet activation and aggregation, atherosclerotic plaque formation, and in the end manifestation of CVD. The risk of any coronary event increases exponentially when two or more risk factors are present. Aside from conventional factors, it has been demonstrated that raised levels of C-reactive protein (CRP), cytokines, homocysteine and fibrinogen are also important promotors of the disease, pointing to partially inflammatory nature of coronary atherosclerosis. The effects of risk factors such as smoking, arterial hypertension and hyperlipidemia on vascular endothelium are proven to be reversible. According to Guidelines on Cardiovascular Disease Prevention in Clinical Practice of the European Society of Cardiology (2007), population is advised to follow the formula 0 3 5 140 5 3 0. It suggests that crucial measures in preserving cardiovascular health are as follows: no smoking (0), walking 3 km daily or 30 minutes of any moderate activity (3), blood pressure less than 140 mm Hg systolic (140), total blood cholesterol less than 5 mmol/L (5), LDL cholesterol less than 3 mmol/L (3), avoidance of overweight and diabetes (0). There are many studies proving the beneficial effects of statins and ACE inhibitors in improving endothelial function and endorsing primary prevention.
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PMID:[Primary prevention of cardiovascular disease]. 1968 67

The identification of endothelial progenitor cells (EPCs) has led to a significant paradigm in the field of vascular biology and opened a door to the development of new therapeutic approaches. Based on the current evidence, it appears that EPCs may make both direct contribution to neovascularization and indirectly promote the angiogenic function of local endothelial cells via secretion of angiogenic factors. This concept of arterial wall repair mediated by bone marrow (BM)-derived EPCs provided an alternative to the local "response to injury hypothesis" for development of atherosclerotic inflammation. Increased oxidant stress has been proposed as a molecular mechanism for endothelial dysfunction, in part by reducing nitric oxide (NO) bioavailability. EPCs function may also be highly dependent on a well-controlled oxidant stress because EPCs NO bioavailability (which is highly sensitive to oxidant stress) is critical for their in vivo function. The critical question is whether oxidant damage directly leads to an impairment in EPCs function. It was revealed that activation of angiotensin II (Ang II) type 1 receptor stimulates nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in the vascular endothelium and leads to production of reactive oxygen species. We observed that Ang II accelerates both BM- and peripheral blood (PB)-derived EPCs senescence by a gp91phox-mediated increase of oxidative stress, resulting in EPCs dysfunction. Consistently, both Ang II receptor 1 blockers (ARBs) and angiotensin converting enzyme (ACE) inhibitors have been reported to increase the number of EPCs in patients with cardiovascular disease. In this review, we describe current understanding of the contributions of oxidative stress in cardiovascular disease, focusing on the potential mechanisms of EPCs senescence.
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PMID:Endothelial progenitor cells dysfunction and senescence: contribution to oxidative stress. 2006 35

Milk-based drinks containing casein-derived tripeptides isoleucine-proline-proline (Ile-Pro-Pro) and valine-proline-proline (Val-Pro-Pro) have been shown to possess antihypertensive and vascular endothelium-protecting properties in hypertensive animal models. Furthermore in clinical intervention trials they reduce blood pressure and arterial stiffness. The exact mechanisms are not known, but inhibition of angiotensin converting enzyme 1 (ACE1) has been suggested mainly to mediate these beneficial effects. The present study investigated the in vitro effects of three tripeptides: Ile-Pro-Pro, Val-Pro-Pro and leqcine-proline-proline (Leu-Pro-Pro) on four renin-angiotensin system enzymes: ACE1, ACE2, chymase, and cathepsin G. Also their effects on arginase I, a critical enzyme in L-arginine-nitric oxide pathway, were studied. It was shown, apparently for the first time, that the inhibitory effects of Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro on ACE1 at micromolar concentrations are competitive in nature. Therefore the efficacy of inhibition is largely dependent on the amount of substrate present. Inhibition of ACE2 and arginase I was reached only at concentrations three orders of magnitude greater. No inhibition of chymase and cathepsin G was observed by the tripeptides. The findings support the hypothesis that Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro act favourably on blood pressure mainly by selective inhibition of ACE1.
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PMID:Effects of milk casein-derived tripeptides Ile-Pro-Pro, Val-Pro-Pro, and Leu-Pro-Pro on enzymes processing vasoactive precursors in vitro. 2048 67

This study describes a modification of Vane's blood-bathed organ technique (BBOT). This new technique consisted of replacing the cascade of contractile smooth muscle organs within the traditional BBOT by a single collagen strip cut from a rabbit's hind leg tendon. Utilizing the extracorporeal circulation of an anesthetized heparinized mongrel cat or Wistar rat, arterial blood was dripped (1-3 ml min(-1)) over a collagen strip. This resulted in a gain in weight of the strip, which was due to the deposition of platelet aggregates and a few blood cells trapped over the strip. Arterial blood that had been used for the superfusion was pumped back into the animal's venous system. However, when this technique is adapted to human volunteers, the superfusing blood should be discarded. In animal experiments, intravenous injections of a variety of classic fibrinolytic agents (e.g., streptokinase) promoted the formation of platelet thrombi. Nitric oxide donors (e.g., SIN-1) at non-hypotensive doses hardly affected the mass of platelet thrombi deposited over the collagen strip, whereas endogenous prostacyclin (e.g., released from vascular endothelium by bradykinin) or exogenous prostacyclin and its stable analogues (e.g., iloprost) dissipated platelet thrombi as measured by a loss in the weight of the blood superfused collagen strip. This model allowed us to assay numerous drugs for their releasing properties of endogenous prostacyclin from vascular endothelium. These drugs included lipophilic angiotensin converting enzyme inhibitors (ACE-Is), which act in vivo as bradykinin potentiating factors (BPF). Other PGI(2)-releasers included statins (e.g., atorvastatin and simvastatin), thienopyridines (e.g., ticlopidine and clopidogrel), a number of thromboxane synthase inhibitors, flavonoids, bradykinin itself, cholinergic M receptor agonists and nicotinic acid derivatives. The thrombolytic actions of lipophilic ACE-Is (e.g., quinapril and perindopril) were prevented by pretreatment with either bradykinin B(2) receptor antagonists (e.g., icatibant) or with endothelial COX-2 inhibitors (e.g., rofecoxib, celecoxib and high dose aspirin). The inhibition of endothelial nitric oxide synthetase (eNOS) by L-NAME hardly blunted the thrombolytic response to ACE-Is. Hence, it can be concluded that many recognized cardiovascular drugs apart from their known basic mechanisms of action, may also behave as releasers of endogenous endothelial prostacyclin. Furthermore, in many instances, this effect may be the primary mechanism of their therapeutic efficacy.
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PMID:Vane's blood-bathed organ technique adapted to examine the endothelial effects of cardiovascular drugs in vivo. 2063 9


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