Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.15 (renin)
 35,795 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral arterial disease (PAD) is associated with significant morbidity and mortality, and yet remains under-recognized and under-treated. Atherosclerosis is the most common cause of lower extremity PAD and pharmacological interventions that alter this central pathogenic role of atherosclerosis may alter the natural history of PAD. There is growing evidence that the renin-angiotensin system (RAS) is a significant mediator of this disease process and that treatment with angiotensin-converting enzyme (ACE) inhibitors is associated with vasculoprotective effects that are independent of the antihypertensive properties of these agents. Numerous lines of evidence suggest that ACE inhibitors directly inhibit the atherosclerotic process and improve vascular endothelial function. In patients with PAD, ACE inhibitors have been shown to improve peripheral circulation as measured by peripheral arterial blood pressure and by increases in peripheral blood flow. Preliminary evidence suggests that ACE inhibitors might improve clinical symptoms in patients with PAD. Recent evidence has confirmed that ACE inhibition is associated with a decrease in morbidity and mortality in patients with arterial disease without left ventricular dysfunction; this benefit was at least as great for the subset of patients with PAD. Overall, these data support a significant role for the RAS in the pathogenesis of all atherosclerotic diseases (including PAD) and suggest that the benefit is independent of the blood pressure lowering properties of these agents. These studies suggest that ACE inhibitor therapy should be considered in the routine management of individuals with PAD, regardless of whether they have hypertension or left ventricular dysfunction.
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PMID:The potential role of angiotensin-converting enzyme inhibition in peripheral arterial disease. 1512 89

Diabetes mellitus affects about 8% of the adult population. The estimated number of patients with diabetes, presently about 170 million people, is expected to increase by 50-70% within the next 25 years. Diabetes is an important component of the complex of 'common' cardiovascular risk factors, and is responsible for acceleration and worsening of atherothrombosis. Major cardiovascular events cause about 80% of the total mortality in diabetic patients. Diabetes also induces peculiar microangiopathic changes leading to diabetic nephropathy conducive to end-stage renal failure, and to diabetic retinopathy that may progress to vision loss and blindness. In terms of major cardiovascular events, coronary heart disease and ischaemic stroke are the main causes of morbidity and mortality in diabetic patients. Peripheral arterial disease frequently occurs, and is more likely to be conducive to critical limb ischaemia and amputation than in the absence of diabetes. Although there are a number of differences in the pathogenesis and clinical features of diabetic macroangiopathy and microangiopathy, these two entities often coexist and induce mutually worsening effects. Endothelial injury, dysfunction and damage are common starting points for both conditions. Causes of endothelial injury can be distinguished into those 'common' to nondiabetic atherothrombosis, such as hypertension, dyslipidaemia, smoking, hypercoagulability and platelet activation; and those more specific and in some cases 'unique' to diabetes and directly related to the metabolic derangement of the disease, such as (i) desulfation of glycosaminoglycans (GAGs) of the vascular matrix; (ii) formation of advanced glycation end-products (AGE) and their endothelial receptors (RAGE); (iii) oxidative and reductive stress; (iv) decline in nitric oxide production; (v) activation of the renin-angiotensin aldosterone system (RAAS); and (vi) endothelial inflammation caused by glucose, insulin, insulin precursors and AGE/RAGE. Prevention of major cardiovascular events with the antithrombotic agent aspirin (acetylsalicylic acid) is widely recommended, but reportedly underutilised in patients with diabetes. However, some data suggest that aspirin may be less effective than expected in preventing cardiovascular events and especially mortality in patients with diabetes, as well as in slowing progression of retinopathy. In contrast, a recent study found picotamide, a direct thromboxane inhibitor, to be superior to aspirin in diabetic patients. Clopidogrel was either equivalent or less active in diabetic versus nondiabetic patients, depending upon different clinical settings.Recent studies have shown that some GAG compounds are able to reduce micro- and macroalbuminuria in diabetic nephropathy, and hard exudates in diabetic retinopathy, but it is as yet unknown whether these agents also influence the natural history of microvascular complications of diabetes. Lifestyle changes and physical exercise are also essential in preventing cardiovascular events in diabetic patients. Available data on the control of the metabolic state and the main risk factors show that careful adjustment of blood sugar and glycated haemoglobin is more effective in counteracting microvascular damage than in preventing major cardiovascular events. The latter objective requires a more comprehensive approach to the whole constellation of risk factors both specific for diabetes and common to atherothrombosis. This approach includes lifestyle modifications, such as dietary changes and smoking cessation and the use of HMG-CoA reductase inhibitors (statins), which are able to correct the lipid status and to prevent major cardiovascular events independently of the baseline lipidaemic or cardiovascular status. Tight control of hypertension is essential to reduce not only major cardiovascular events but also microvascular complications. Among antihypertensive measures, blockade of the RAAS by means of ACE inhibitors or angiotensin II receptor antagonists recently emerged as a potentially polyvalent approach, not only for treating hypertension and reducing cardiovascular events, but also to prevent or reduce albuminuria, counteract diabetic nephropathy and lower the occurrence of new type 2 diabetes in individuals at risk.
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PMID:Approaches to prevention of cardiovascular complications and events in diabetes mellitus. 1748 45

Peripheral arterial disease is a result of atheroma. This disease is frequent in subjects with vascular risk factors. This disease is also frequent in low income countries. The detection and the diagnosis of peripheral arterial disease is obtained by calculating the ankle brachial index. Patients with peripheral arterial disease are not always symptomatic thus explaining how this disease is under diagnosed. The symptoms can be absent, and especially in case of diabetes or in women. In case of peripheral arterial disease, atheroma often involves other arterial vascular networks especially the coronaries. An adapted treatment reduces the morbi-mortality linked to this disease. This treatment is based on the correction of the vascular risk factors and especially tobacco cessation, walking rehabilitation and drugs (antiplatelet agent, statin, renin angiotensin system blocker). In case of rest or critic ischemia, the first-line treatment is a revascularisation. In peripheral arterial disease, management of patients is often non optimal and therapeutic targets fairly often obtained.
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PMID:[Lower-limb peripheral arterial disease]. 3235 79