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)

Metabolic syndrome represents a common risk factor for premature cardiovascular disease and cancer whose core cluster includes diabetes, hypertension, dyslipidaemia and obesity. The liver is a target organ in metabolic syndrome patients in which it manifests itself with non-alcoholic fatty liver disease spanning steatosis through hepatocellular carcinoma via steatohepatitis and cirrhosis. Given that metabolic syndrome and non-alcoholic fatty liver disease affect the same insulin-resistant patients, not unexpectedly, there are amazing similarities between metabolic syndrome and non-alcoholic fatty liver disease in terms of prevalence, pathogenesis, clinical features and outcome. The available drug weaponry for metabolic syndrome includes aspirin, metformin, peroxisome proliferator-activated receptor agonists, statins, ACE (angiotensin I-converting enzyme) inhibitors and sartans, which are potentially or clinically useful also to the non-alcoholic fatty liver disease patient. Studies are needed to highlight the grey areas in this topic. Issues to be addressed include: diagnostic criteria for metabolic syndrome; nomenclature of non-alcoholic fatty liver disease; enlargement of the clinical spectrum and characterization of the prognosis of insulin resistance-related diseases; evaluation of the most specific clinical predictors of metabolic syndrome/non-alcoholic fatty liver disease and assessment of their variability over the time; characterization of the importance of new risk factors for metabolic syndrome with regard to the development and progression of non-alcoholic fatty liver disease.
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PMID:Review article: the metabolic syndrome and non-alcoholic fatty liver disease. 1622 69

The incidence of type-2 diabetes is increasing throughout the world. By 2010, 350 million people will have this disease. Microalbuminuria is present in more than one third, for some at diabetes diagnosis. Rather than a complication, it is an indication of a vascular disorder that is part of the metabolic syndrome. 25% will develop end-stage kidney failure. Several studies have identified microalbuminuria or proteinuria as an independent cardiovascular risk factor. Others have shown that antihypertensive treatments acting on the renin-angiotensin system (ACE inhibitors, ARBs agents) can reduce the progression of nephropathy in people with hypertension, type 2 diabetes and microalbuminuria. The "nephroprotective" effects of these drug classes, beyond their role in blood-pressure reduction, are suggested by modifications in renal structure and protein expression. But no study has so far examined their value in primary prevention in persons with type 2 diabetes without--but at risk of developing--microalbuminuria. The Roadmap study (Randomized Olmesartan And Diabetes Microalbuminuria Prevention Study) of primary prevention has as its objective measurement of the impact of ARBs (olmesartan 40 mg/d) treatment on renal outcome in 4400 patients with type 2 diabetes without microalbuminuria. Follow-up of this placebo-controlled study will last for 5 years. Conducted in 200 European centers, its results are expected for 2012.
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PMID:[Primary cardiorenal prevention in patients with type-2 diabetes. The Roadmap study]. 1626 93

Pure allicin, prepared biosynthetically by reacting synthetic alliin with an immobilized alliinase enzyme, is known to possess cardioprotective effects. However, in its pure form, allicin is pharmacologically unstable. S-allylmercaptocaptopril (CPSSA) is a new stable synthetic compound produced by chemical reaction between allicin and the angiotensin converting enzyme inhibitor captopril. Using the fructose-induced metabolic syndrome rat model we studied the effects of short-term treatment with two doses of CPSSA on cardiovascular risk factors associated with the metabolic syndrome, in comparison to the effects of allicin and captopril separately. Allicin (8 mg/(kg day)) significantly reduced insulin, triglycerides, and homocysteine concentrations, and had a slight effect on SBP. Captopril (50mg/(kg day)) only improved blood pressure and homocysteine. Treatment with low dose of CPSSA (5mg/(kg day)) lowered SBP but did not improve any other measured parameter, while treatment with a higher dose (50mg/(kg day)) significantly decreased blood pressure, triglycerides, and homocysteine concentrations. We conclude that the combined molecule CPSSA integrates the anti-hypertensive, lipid-lowering, and homocysteine-reducing effects of both allicin and captopril, making it a potential cardiovascular protective agent.
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PMID:The effects of S-allylmercaptocaptopril, the synthetic product of allicin and captopril, on cardiovascular risk factors associated with the metabolic syndrome. 1628 91

The diagnostic categories of impaired glucose tolerance (IGT) and impaired fasting glucose (IFG) were stablished in an effort to identify populations at risk for developing type 2 diabetes mellitus (T2DM). Both IGT and IFG are associated with increased risk of developing T2DM, but recent analyses found that the thresholds of risk vary among different populations and an even lower diagnostic threshold of IFG may be appropriate. IGT has been linked with an increased risk of cardiovascular events and some analyses have demonstrated an increased mortality risk compared with patients with normal glucose tolerance. In contrast, a continuum of increased risk of microvascular manifestations of T2DM has been demonstrated with IFG but an association of IFG with cardiovascular events has not been well established. Although both IGT and IFG are associated with resistance to insulin and increased insulin secretion, they do not identify the identical patient populations and are not equivalent in predicting development of T2DM or cardiovascular events. IFG and IGT have been associated with other features of insulin resistance, including dyslipidaemia, hypertension, abdominal obesity, microalbuminuria, endothelial dysfunction, and markers of inflammation and hypercoagulability, traits collectively referred to as the metabolic syndrome. Analyses of combinations of these components have also been associated with progression to T2DM, cardiovascular disease and increased mortality. The foundation of treatment for IGT, IFG, and the metabolic syndrome is lifestyle modification, including both dietary change and routine exercise. To date, several clinical trials have found that lifestyle modification is the most efficacious strategy to prevent progression to T2DM. Alternative treatments include pharmacotherapy with metformin or acarbose, both of which have been demonstrated to decrease the development of T2DM. Ongoing clinical trials are evaluating newer pharmacotherapies, including angiotensin converting enzyme inhibitors, angiotensin receptor antagonists, metglitinides and thiazolidinediones, to prevent both T2DM and cardiovascular events. In combination with lifestyle modification, these therapies offer hope for effective prevention of T2DM and its consequences in high-risk patients.
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PMID:Impaired glucose tolerance and impaired fasting glucose--a review of diagnosis, clinical implications and management. 1630 67

Moexipril (7.4-15 mg/day) was given to 34, spirapril (3-6 mg/day) -- to 18 postmenopausal women with hypertension and metabolic syndrome for 16 weeks. Hydrochlorthiazide was added when therapy was not sufficiently effective. Both angiotensin converting enzyme inhibitors had similar hypotensive activity: blood pressure normalized in 71 and 61% of moexipril and spirapril treated women, respectively. Both drugs promoted normalization of metabolism of lipid (lowering of levels of cholesterol, atherogenic lipoproteins and triglycerides) and carbohydrates (lowering of hyperinsulinemia). Patients with postmenopausal metabolic syndrome had elevation of leptin level up to 27.5+/-5.5 pg/ml. Moexipril and spirapril caused lowering of elevated levels of leptin. These drugs did not affect levels of sex hormones. They exerted vasoprotective (normalization of endothelium dependent and independent vasodilatation) and nephroprotective (attenuation and normalization of microalbuminuria) effects. Thus spirapril and moexipril are effective in treatment of hypertension in patients with postmenopausal metabolic syndrome.
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PMID:[Comparative efficacy and safety of contemporary Angiotensin converting enzyme inhibitors moexipril and spirapril in women with postmenopausal metabolic syndrome]. 1647 9

Although the year 2005 has reinforced the therapeutic advances of 2004, with confirmation of certain concepts, the 'coxib affair' has continued to provoke arguments between pharmaceutical companies, licensing agencies as well as patients, some of whom have amalgamated into consumer groups to reject en masse placing any responsibility on the prescribers in favour of an attack on the drug licensing process itself. Among the cardiovascular drugs that will soon be licensed, only ivabradine in stable angina, and remodulin in primary pulmonary arterial hypertension are new. The therapeutic advances in 2005 regarding platelet aggregation and blood coagulation have been significant, in the human, scientific and commercial context, while hypertension has not been ignored. Another new development is the ever more precise notion of the metabolic syndrome, a target of choice for the pharmaceutical industry. The potential range of applications has been widened to include obesity, hypertension, diabetes, HDL cholesterol... The licensing authorities find themselves facing a hurdle to overcome, with novel combinations of drugs (ACE inhibitors, calcium blockers/statins, statins/aspirin, ARA2/calcium blockers...).
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PMID:[The best of clinical cardiovascular pharmacology in 2005]. 1647 71

The biological actions of angiotensin II (ANG), the most prominent hormone of the renin-angiotensin-aldosterone system (RAAS), may promote the development of atherosclerosis in many ways. ANG aggravates hypertension, metabolic syndrome, and endothelial dysfunction, and thereby constitutes a major risk factor for cardiovascular disease. The formation of atherosclerotic lesions involves local uptake, synthesis and oxidation of lipids, inflammation, as well as cellular migration and proliferation--mechanisms that may all be enhanced by ANG via its AT1 receptor. ANG may also increase the risk of acute thrombosis by destabilizing atherosclerotic plaques and enhancing the activity of thrombocytes and coagulation. After myocardial infarction, ANG promotes myocardial remodeling and fibrosis, and its many pathological mechanisms deteriorate the prognosis of these high-risk patients in particular. Therapeutically, inhibitors of the angiotensin I-converting enzyme (ACEI) and AT1 receptor blockers (ARB) are available to suppress the generation and cellular signaling of ANG, respectively. Despite major differences in the efficacy of ANG suppression and the modulation of other hormones and receptors, both classes of drugs are generally effective in attenuating numerous pathomechanisms of ANG in vitro, and in diminishing the development of atherosclerotic lesions and restenosis after angioplasty in various animal models. In clinical therapy, ACEI and ACE are well-tolerated antihypertensive drugs that also improve the prognosis of heart failure patients. After myocardial infarction and in stable coronary heart disease, ACEI have been shown to reduce mortality in a manner independent of hemodynamic alterations. However, there is little evidence that inhibitors of the RAAS may be effective against arterial restenosis, and a possible benefit of these substances compared to other antihypertensive drugs in the primary prevention of coronary heart disease in hypertensive patients is still a matter of debate, possibly depending on the specific substance and condition being investigated. As such, the general clinical efficacy of ACEI and ARB may be due to a positive influence on hemodynamic load, vascular function, myocardial remodeling, and neuro-humoral regulation, rather than to a direct attenuation of the atherosclerotic process. Further therapeutic advances may be achieved by identifying optimum drugs, patient populations, and treatment protocols.
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PMID:ACE inhibitors and angiotensin II receptor antagonists. 1659 9

Patients with type 2 diabetes often also exhibit additional features of the metabolic syndrome. These include specifically central obesity triggering development and maintenance of diabetes together with arterial hypertension, hypertriglyceridemia and low levels of high-density lipoprotein cholesterol. Chronic therapy of the metabolic syndrome in diabetics after coronary bypass surgery focuses on changes in lifestyle, i.e., cessation of smoking, changes in nutrition and increase in physical activity. Nutrition aims at fat reduction and modification to reduce saturated fatty acids, to allow mono- and polyunsaturated fatty acids instead, and moderate alcohol consumption. High fiber and complex carbohydrate diet complete the recommendations. Nutrition therapy connected to increases in physical activity are aimed at reducing weight in overweight and obese subjects, which should reduce their body weight by 5 to 10% within about 6 months. Normal weight subjects benefit from increases in physical activity by lipid and glucose regulation as well as by reduction in mortality.Diabetes-specific therapy aims at normoglycemia including postprandial blood glucose levels, reduces blood pressure supported by ACE inhibitors and aims at weight reduction. Reduction of LDL-cholesterol is the first line therapy, also diminishing small-dense LDL particles. Decreasing triglycerides and increasing HDL-cholesterol are further lipid-regulating aims. Specifically diabetics after coronary bypass surgery need LDL-cholesterol levels below 70 mg/d (1.8 mmol/L) and triglycerides below 150 mg/dL (1.7 mmol/L). In addition, in males HDL-cholesterol should be at least above 40 mg/dl (1 mmol/L), in females above 50 mg/dL (1.3 mmol/L).
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PMID:[Long-standing therapy of the metabolic syndrome in diabetics after coronary artery bypass surgery]. 1659 37

Since the 1950s the definition of the aggregate of metabolic disorders possibly presenting with adult obesity has evolved without reaching a unifying agreement on what metabolic syndrome is. After years of consensus on and research into identifying the extent to which certain criteria of metabolic syndrome may be predisposing factors for cardiovascular events, a reverse shift can be noticed in recent studies raising numerous points of contention about various elements that may be diagnostic for the syndrome. Of these, one of the most tenuous is probably arterial hypertension. Uncertainties have emerged regarding the arbitrariness of cut-off values, which differ according to the classification system the study applied, the methods of measurement, and the dilemma of hyperinsulinemia/insulin resistance which is present in only 50-60% of individuals with hypertension. Currently available data fail to solve these conundrums; however, some studies have correlated hypertension and dislipidemia with an increased risk of cardiovascular events. International epidemiologic data indicate that the prevalence of the syndrome varies between populations and between the sexes within the same populations, suggesting that diagnostic criteria need to take better account of ethnic group origin. Prevention of metabolic syndrome is still based on lifestyle changes; the huge risk of an imminent pandemic has called the attention of the American Heart Association to the importance of prevention and early treatment of the pediatric population--a new segment at risk of early cardiovascular events. Pharmacological therapy is directed at controlling various risk factors, particularly hypertension and metabolic disturbances. ACE inhibitors, sartans and statins are currently the drugs of first choice in treating metabolic syndrome.
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PMID:[Metabolic syndrome and hypertension: prevention and treatment]. 1676 Aug 51

Type 2 diabetes and atherosclerotic vascular disease develop in parallel. Prospective epidemiologic studies have shown a striking communality of major risk factors for both diseases. This raises the question of a "common soil". The traits of the metabolic syndrome including dyslipidemia, visceral obesity and hypertension are predictors of type 2 diabetes as well as coronary heart disease. The same applies to the environmental factors: overnutrition, physical inertia and smoking. Visceral obesity, insulin resistance and low-grade inflammation are known as major components of the common soil for metabolic syndrome and coronary heart disease. Depending on the quality of metabolic control diabetes will accelerate the progression of atherosclerosis via unstable plaque formation. The "common soil" concept provides a paradigm for an integrated therapeutic approach. This applies to a lifestyle intervention as well as a rational use of drugs in diseases of the metabolic syndrome. The medication should consider coexisting disorders of the metabolic syndrome to use pleiotropic effects. On the other hand, side effect such as the worsening of blood glucose levels caused by beta-blockers and diuretics should be avoided. The following medication should be preferred in context of the metabolic syndrome: oral antidiabetics such as acarbose, metformin and thiazolidinediones, antihypertensives such as ACE inhibitors and ARBs (angiotensin receptor blockers) and lipid-lowering drugs such as atorvastatin, rosuvastatin, and the modern nicotinic acid derivative Niaspan, respectively. The strategy using synergies in drug treatment can reduce polypharmacy and costs and improve the patients' compliance.
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PMID:[Metabolic syndrome: "common soil" for diabetes and atherosclerosis. Novel approaches to an integrated therapy]. 1677 May 62


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