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)

Some 44% of all patients with elevated blood pressure are overweight. In obesity-related hypertension, sympathicotonia is regularly found, together with elevated intracellular calcium, sodium retention, increased cardiac output (per minute) and a sensitivity to salt. The role played by hyperinsulinemia has apparently been overstated. A primary rise in the minimal vascular resistance suffices to reduce the perfusion of the skeletal musculature and, solely on this basis, to induce insulin resistance. For the treatment of obesity-related hypertension, non-medicinal approaches to weight reduction predominate. Reducing the daily salt intake to 5 g can also bring about a measurable reduction in blood pressure. For the treatment with antihypertensive drugs, beta blockers and diuretics are the initial choice; in the case of pronounced metabolic syndrome, ACE-inhibitors and alpha-1 receptors.
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PMID:[Fat control--an effective antihypertensive strategy. Special recommendations for therapy of the overweight patient]. 1079 42

We report two cases, which underwent surgery through Median sternotomy. They were on ACE inhibitors [corrected] pre-operatively. Both of these patients developed persistent dry cough post-operatively, which resulted in sternal wound dehiscence. They had no clinical or bacteriological evidence of sternal wound infection. Although one patient was overweight and had moderately impaired left ventricular function, there were no other associated risk factors. Both patients underwent rewiring of the sternum. Type II receptors inhibitor were introduced post-rewiring, which cured the persistent dry cough. Both the patients are enjoying a good quality of life at 2 year 6 months and 2 years post-rewiring of the sternum.
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PMID:Sternal dehiscence after cardiac surgery and ACE inhibitors [correction of ACE type 1 inhibition]. 1178 93

It is well established that blood pressure lowering is effective for the primary prevention of stroke and other cardiovascular disorders in subjects with blood pressures as low as 140/90 mmHg, and up to 80 years of age. Despite this knowledge, blood pressure levels are controlled in less than 25% of the hypertensive population worldwide. It has taken longer to prove that blood pressure lowering is equally effective for the prevention of recurrent stroke. The results of PROGRESS (Perindopril Protection Against Recurrent Stroke Study) have confirmed that a perindopril-based regimen in subjects with cerebrovascular disease substantially reduces the incidence of secondary stroke and primary myocardial infarction. It is daunting to recall that it has taken almost two decades for beta-blockers to be widely used for the secondary prevention of myocardial infarction, since widespread use of the PROGRESS regimen would prevent more than half a million strokes worldwide each year. The real challenge now is to implement novel and effective strategies for the control of blood pressure and other cardiovascular risk factors worldwide. Strategies should include lifestyle measures, such as stopping smoking, exercise and reducing overweight. There is a real need to identify hypertensive subjects and treat them with blood pressure lowering drugs for primary prevention. In subjects with established cardiovascular disease, consideration should be given to a range of proven interventions for secondary prevention, such as blood pressure lowering, irrespective of current blood pressure, anti-platelet drugs, statins for lowering cholesterol and glycaemic control in diabetics. Among new strategies to lower overall cardiovascular risk, consideration should be given to the development of single-pill combinations of drugs of known efficacy, including various combinations of ACE inhibitors, diuretics, beta-blockers, aspirin and statins, among others.
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PMID:Challenges for the prevention of primary and secondary stroke: the importance of lowering blood pressure and total cardiovascular risk. 1182 38

Hypertension is a risk factor for cardiovascular and renal organ damage. Environmental conditions affect the development of high blood pressure (BP), although genetic influences are also important. Current international guidelines recommend reducing dietary sodium to no more than 100 mmol (about 2.4 g sodium or approximately 6 g salt) per day to prevent BP rising; the current intake of sodium in industrialized countries is approximately double the recommended amount. Clinical trials (DASH and TOHP studies) have shown that dietary factors are fundamental in the prevention and control of BP. Low dietary sodium intake is particularly effective in preventing hypertension in subjects with an increased risk such as the overweight, borderline hypertensives or the elderly. A low-salt diet combined with anti-hypertensive therapies facilitates BP reduction independent of race. The hypotensive effect of calcium channel blockers is less dependent on salt intake than other drugs, such as ACE inhibitors or diuretics. Reduced sodium intake associated with other dietary changes (such as weight loss, and increasing potassium, calcium and magnesium intake) are important instruments for the prevention and therapy of hypertension.
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PMID:Salt intake and hypertension therapy. 1193 20

To evaluate the expression of the renin-angiotensin system (RAS) genes in visceral (VAT) and subcutaneous adipose tissue (SAT) in normotensive subjects with different body mass index (BMI). Adipose tissue was obtained from 22 normotensive (12 normal weight and 10 overweight) patients during surgery for colecystectomy. Angiotensinogen (AGT), angiotensin II receptor type 1 (AT1), angiotensin converting enzyme (ACE) mRNA, and protein levels were measured by reverse transcriptase-polymerase chain reaction and Western blot analysis, respectively. The AGT mRNA and AT1 receptor mRNA levels were significantly higher in VAT than in SAT; AGT mRNA levels were higher, although not significantly, in overweight subjects in both SAT and VAT. There was no significant difference in ACE gene expression in the two tissues, and no expression of angiotensin II receptor type 2 (AT2). Finally, we failed to find mRNA for the renin gene in adipose tissue. The presence of AGT and ATI receptor in SAT and VAT was confirmed by Western blot analysis. Our study demonstrates the presence--and different levels of expression--of the various components of the RAS system (AGT, ATI, and ACE) in human SAT and VAT, and highlights the different role and regulation of the system in the two tissues. Its high expression in VAT suggests that its regulation and function are involved in all conditions where visceral adiposity is present.
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PMID:Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. 1202 38

Arterial hypertension and diabetes are potent independent risk factors for cardiovascular, cerebral, renal and peripheral (atherosclerotic) vascular disease. The prevalence of hypertension in diabetic individuals is approximately twice that in the non-diabetic population. Diabetic individuals with hypertension have a greater risk of macrovascular and microvascular disease than normotensive diabetic individuals. Hypertension is a major contributor to morbidity and mortality in diabetes, and should be recognized and treated early. Type 2 diabetes and hypertension share certain risk factors such as overweight, visceral obesity, and possibly insulin resistance. Life-style modifications (weight reduction, exercise, limitation of daily alcohol intake, stop smoking) are the foundation of hypertension and diabetes management as the definitive treatment or adjunctive to pharmacological therapy. Additional pharmacological therapy should be initiated when life-style modifications are unsuccessful or hypertension is too severe at the time of diagnosis. All classes of antihypertensive drugs are effective in controlling blood pressure in diabetic patients. For single-agent therapy, ACE-inhibitors, angiotensin receptor blocker, beta-blockers, and diuretics can be recommended. Because of concerns about the lower effectiveness of calcium channel blockers in decreasing coronary events and heart failure and in reducing progression of renal disease in diabetes, it is recommended to use these agents as second-line drugs for patients who cannot tolerate the other preferred classes or who require additional agents to achieve the target blood pressure. The choice depends on the patients specific treatment indications since each of these drugs have potential advantages and disadvantages. In patients with microalbuminuria or clinical nephropathy, both ACE-inhibitors and angiotensin receptor blockers are considered first line therapy for the prevention of and progression of nephropathy. Since treatment is usually life-long, cost effectiveness should be included in treatment evaluation.
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PMID:[Treatment of hypertension in type 2 diabetes mellitus--2002 update]. 1223 35

Experimental studies have demonstrated that proteins filtered by the glomerulus induce a proliferation of proximal tubular cells accompanied by an increased synthesis of many vasoactive and proinflammatory substances. The appearance of interstitial cellular infiltrates, a well-known finding in proteinuric diseases, precedes progressive tubulointerstitial fibrosis. Activation of the transcription factor kappaB (NF-kappaB) plays a pivotal role in the renal damage induced by proteinuria. In this scenario, any therapeutic intervention that reduces proteinuria should be beneficial for the kidney. Drugs that block the renin-angiotensin system [angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor antagonists (ARA)] have repeatedly shown striking antiproteinuric and renoprotective properties, both in experimental and clinical studies. Studies in patients with type 1 and type 2 diabetic nephropathy as well as in non-diabetic nephropathies have confirmed that the renoprotection obtained with ACEI/ARA is closely related with their antiproteinuric effect and is largely independent of blood pressure changes. However, resistance to the antiproteinuric effect of ACEI/ARA is a common clinical observation. Several therapeutic measures (that is, adequate blood pressure control, early introduction of ACEI/ARA, dietary protein restriction, low salt diets, weight loss in overweight patients, addition of a diuretic, increasing ACEI/ARA dose titrated against proteinuria levels, combined therapy ACEI plus ARA, addition of drugs with antiproteinuric effect such as non-dihydropiridine calcium channel blockers or NSAIDs) may increase the proteinuria reduction induced by ACEI and ARA.
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PMID:Renal damage associated with proteinuria. 1241 Aug 54

The management of hypertension in the overweight and obese patient is a frequently encountered but under investigated clinical problem. The conventional management of such patients involves weight reduction with dietary therapy or a combined approach with dietary and anti-obesity drug therapy. However, long-term weight reduction, which is necessary to sustain blood pressure (BP) control, is not feasible in over 80% of patients. Anti-obesity therapy with orlistat has inconsistent effects on BP and may benefit only patients who have uncontrolled or non-medicated hypertension. Anti-obesity therapy with sibutramine may be associated with a modest worsening of BP control. Consequently, antihypertensive drug therapy is often required to supplement a weight reduction programme, and also in patients with severe hypertension or hypertension-associated end-organ damage. Treatment with a thiazide diuretic should be considered as first-line antihypertensive drug therapy in overweight and obese patients. ACE inhibitors or non-dihydropyridine calcium channel antagonists are reasonable alternatives where clinically indicated, or they can be used in combination with a thiazide diuretic if treatment with the diuretic alone is insufficient. If such treatment is inadequate for BP control, the addition or substitution of an alpha- or beta-adrenoceptor antagonist may be considered, although the latter can be associated with weight gain. Concurrent disease is an important determinant of first-line and supplementary antihypertensive drug therapy. Additional studies are needed to determine the long-term (>1 year) efficacy and safety of antihypertensive and anti-obesity management strategies in the overweight and obese hypertensive patient.
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PMID:The management of hypertension in the overweight and obese patient: is weight reduction sufficient? 1516 30

Few and contrasting data are available on the presence of a thrombophilic state in patients with retinal vein occlusion (RVO), and we have previously demonstrated a role of elevated PAI-1 activity as a risk factor for this condition. The present study was undertaken to investigate whether PAI 4G/5G and ACE I/D polymorphisms are independent risk factors for RVO and whether they account for elevated PAI-1 activity levels. We studied 112 RVO patients (52 males and 60 females; range 18-83 years; median age 60 years) and 112 healthy subjects (52 males and 60 females; range 20-84 years; median age 57 years). PAI-1 activity was determined by a chromogenic assay and ACE I/D and PAI-1 4G/5G polymorphisms by polymerase chain reaction (PCR) and restriction length fragment polymorphism (RLFP) methods. Elevated PAI-1 activity (above 95(th) percentile of the controls) was significantly associated with RVO at multivariate analysis after adjustment for age, sex, traditional cardiovascular risk factors and haemostasis-related risk factors (OR = 4.93, 95% CI 1.70-14.30; p = 0.003). The homozygosity for ACE DD was found to be an independent risk factor for RVO at multivariate analysis (OR = 1.98, 95% CI 1.01-3.83; p = 0.049), whereas no significant association between homozygosity for PAI-1 4G4G and risk of RVO was observed. Subjects carrying both ACE DD genotype and PAI-1 4G4G genotype showed an increased risk for RVO at multivariate analysis (OR = 4.82, 95% CI 1.89-12.29; p = 0.001). In 45/112 patients without the established risk factors for RVO (hyper-tension, hypercholesterolemia and diabetes) or characteristics known to be associated to increased PAI-1 activity (overweight, hypertriglyceridemia, and smoking habit) the contemporary presence of ACE DD and PAI-1 4G4G genotype was significantly associated with a risk for RVO (OR = 8.26, 95% CI 1.18-57.92; p = 0.034). In conclusion, in our study: 1-indicates that ACE DD genotype is a risk factor for RVO in the whole group of patients, and in the subgroup of patients without the established risk factors for RVO or characteristics influencing the PAI-1 activity, when associated to PAI-1 4G4G genotype, and 2-confirms the role of hypofibrinolysis, documented by high levels of PAI-1 activity, in the occurrence of patients with RVO.
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PMID:Impaired fibrinolysis in retinal vein occlusion: a role for genetic determinants of PAI-1 levels. 1521 45

Moxonidine is a centrally active imidazoline receptor agonist that effectively lowers blood pressure and has been shown to have beneficial effects on lipid and carbohydrate metabolism. We assessed the efficacy of moxonidine in a postmarketing surveillance study (CAMUS) conducted in 772 practices in Germany, documenting 4005 patients with hypertension, who were overweight and/or suffered from metabolic syndrome. Patients were treated with moxonidine (Cynt) for the first time following the baseline visit for 8 weeks. Mean blood pressure decreased from 168/97 to 141/83 mmHg for all patients and from 168/96 to 141/83 mmHg for patients with metabolic syndrome. Blood pressure reduction was particularly pronounced in patients with severe hypertension at baseline. The response rate (DBP< or =90 mmHg or reduction > or =10 mmHg) of antihypertensive treatment with moxonidine was 94.0% for all patients and 93.8% for patients with metabolic syndrome. The recommended targets for antihypertensive treatment of the German Diabetes Society/German Hypertension Society were reached by 30.5% of nondiabetics (goal: <140/90 mmHg) and by 3.6% of diabetics (goal: <130/80 mmHg) observed. After 8 weeks of treatment, patients achieved a mean weight loss of 1.4 kg, which was particularly pronounced in obese patients. The rate of patients receiving antihypertensive combination therapy was 81.1% for those with metabolic syndrome, and 63.3% for all other patients. Patients with metabolic syndrome were preferentially treated with ACE inhibitors and diuretics. We conclude that moxonidine effectively reduces blood pressure in patients with metabolic syndrome while simultaneously reducing body weight in obese patients.
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PMID:Moxonidine in the treatment of overweight and obese patients with the metabolic syndrome: a postmarketing surveillance study. 1526 5


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