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 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increasing number of diabetic patients develop different stages of renal failure. However, often an inappropriate parameter, the serum creatinine is measured as a marker of glomerular function. Calculated glomerular filtration rate or endogenous creatinine clearance are suggested to be used for the estimation of the glomerular function. Important structures preventing proteinuria in the kidney are glomerular basement membrane, podocytes and proximal tubular cells. In diabetes mellitus loss of nephrin of podocytes can play a role in the development of microalbuminuria, and podocyte desquamation may result in the progression to proteinuria. In diabetes mellitus there is an increased formation of advanced glycation endproducts (AGE), of which the only elimination organ is the kidney. The AGE induce proteinuria and atherosclerosis. Therefore, in diabetes mellitus a vicious circle develops due to proteinuria, nephron loss and accumulation of AGE, which play a role in the initiation and progression of diabetic nephropathy and atherosclerosis. Angiotensin converting enzyme inhibitors and angiotensin receptor blockers having antiproteinuric effect may decrease the risk of diabetic nephropathy and atherosclerosis. Improvement of carbohydrate metabolism with a consequential decrease in the formation of AGE is an important contributor to the prevention and treatment of diabetic nephropathy and atherosclerosis.
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PMID:Prevention and treatment of diabetic nephropathy. 1595 73

Type 2 diabetes is increasingly common worldwide and is beginning to strike younger age groups. Almost 90% of all patients with diabetes show insulin resistance, which also precedes the first symptoms of diabetes. The mechanisms underlying the development of insulin resistance are not well understood. In recent years, several studies have been published that implicate subclinical chronic inflammation as an important pathogenetic factor in the development of insulin resistance and type 2 diabetes. This opens new perspectives for diagnosis and treatment of early insulin resistance and incipient glucose intolerance. Surrogate markers for this low-grade chronic inflammation include CRP, IL-6 and TNF-alpha. Some antidiabetic agents, for example, glitazones that reduce insulin resistance, and insulin itself, reduce inflammation. Conversely, antiinflammatory drugs (ASA/NSAID) may improve glucose tolerance. Vasoactive drugs that are often prescribed to people with diabetes, for example, statins and ACE inhibitors/angiotensin receptor antagonists, also counteract inflammation and reduce the risk of type 2 diabetes. More specific and sensitive biomarkers should be identified, which may predict early disturbances in insulin sensitivity and cardiovascular risk. Also, inflammatory signalling pathways need to be explored in greater detail, and may form the basis of drugable targets against the epidemic of insulin resistance and atherosclerosis.
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PMID:Inflammation and the etiology of type 2 diabetes. 1599 Dec 54

Type 2 diabetes is a cardiovascular disease equivalent that is associated with accelerated atherosclerosis and significant mortality. However, the metabolic syndrome and prediabetes are associated with increased cardiovascular mortality, indicating that atherogenic vascular changes begin prior to the onset of overt diabetes. At the core of diabetes and the metabolic syndrome is insulin resistance (IR), which sets the stage for dyslipidemia, hypertension, and inflammation. Endothelial dysfunction is the first stage of the atherosclerosis process and results from exposure to cardiovascular risk factors, such as IR and diabetes. IR and atherosclerosis follow parallel paths as they progress in severity. Thiazolidinediones, angiotensin-converting enzyme inhibitors, angiotensin receptor-AT1 blockers, and statins are widely used in the treatment of diabetes. Emerging evidence indicates that these pharmacologic agents have added mechanisms of action, especially on the endothelium and in the prevention of diabetes.
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PMID:Insulin resistance and the endothelium. 1603 73

Renal artery stenosis is a common problem, particularly for patients with other manifestations of atherosclerosis. Wide practice variations are apparent regarding how best to manage this disorder. Part of this variation is based on a broad range of clinical presentation, from incidentally identified disease of no clinical importance to rapidly progressive hypertension, renal failure, and refractory congestive heart failure. Advances in antihypertensive therapy, particularly as a result of angiotensin-converting enzyme inhibition and angiotensin receptor blockade, have led to improved blood pressure control and delayed recognition of renal artery disease. As a result, patients now sent for revascularization are older than before and have high comorbid disease risk, primarily related to cardiovascular events. Clinicians need to be vigilant for evidence of unsuspected renal artery stenosis as a cause of treatment-resistant hypertension and/or renal failure. Renal revascularization should be considered in viable individuals before the development of advanced renal insufficiency.
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PMID:Atherosclerotic renal artery stenosis: how big is the problem, and what happens if nothing is done? 1625 47

Endothelium is not a mere monolayer of cells separating flowing blood and vascular wall, but plays a key role in maintenance of vascular homeostasis. Nitric oxide is the principal mediator of endothelial function; it is a potent vasodilator, it inhibits platelet aggregation, vascular smooth muscle cell migration and proliferation, and monocytes adhesion. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by impairment of endothelium-dependent vasodilation (EDV) and by pro-coagulant/pro-inflammatory endothelial activities. The assessment of EDV is a common parameter for testing endothelial function. EDV in the coronary arteries is angiographically evaluated by measurement of the vessel response to endothelial agonists, such as acetylcholine. A non-invasive technique for the detection of EDV employs the ultrasound evaluation of flow-mediated dilation (FMD) of the brachial artery following reactive hyperemia. A close relation between FMD and coronary vasomotor response to acetylcholine has been demonstrated. Endothelial dysfunction in the coronary circulation may precede development of angiographically evident coronary atherosclerosis; endothelial dysfunction has been also associated with a higher prevalence of coronary artery disease and resulted predictive of future cardiovascular events; recently, it has been associated with a higher risk of restenosis after coronary stent implantation. Endothelial dysfunction is actually considered a reversible phenomenon; drug therapies with ACE-inhibitors, angiotensin receptor blockers, statins, antioxidants agents have shown a beneficial effect on endothelial function.
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PMID:[The role of endothelial dysfunction in the pathogenesis and in clinical practice of atherosclerosis. Current evidences]. 1649 75

The metabolic syndrome is characterized by the clustering of insulin resistance, dyslipidemia, and hypertension and is associated with increased risk of cardiovascular disease and type 2 diabetes mellitus. However, older antihypertensive agents such as thiazide diuretics and beta-blockers have potentially adverse effects on glucose and lipid metabolism and may even the exacerbate the metabolic syndrome and increase risk of type 2 diabetes. Recent clinical trials have suggested that antihypertensive agents that inhibit the renin-angiotensin system may reduce risk for new-onset type 2 diabetes, but only a few of these studies were placebo controlled, and in most cases, the absolute antidiabetic effects were relatively modest. Evidence is accumulating that telmisartan, in addition to blocking the angiotensin II type 1 receptor, activates the peroxisome proliferator-activated receptor (PPAR)-gamma a well-known target for treatment of the metabolic syndrome and diabetes. By contrast, other angiotensin-receptor blockers are largely devoid of activity on PPAR-gamma. Telmisartan is a partial agonist of PPAR-gamma and has a superior tolerability profile without causing the fluid retention and edema associated with full agonists of PPAR-gamma such as pioglitazone and rosiglitazone. Recent studies have indicated that in addition to antidiabetic properties, PPAR-gamma activators may also provide protection against atherosclerosis and coronary events. Thus, the ability of telmisartan both to activate PPAR-gamma and to block the angiotensin receptor may provide added value not only in the treatment of the metabolic syndrome and prevention of type 2 diabetes but also in prevention and treatment of atherosclerotic cardiovascular disease.
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PMID:New treatment strategies for patients with hypertension and insulin resistance. 1656 44

Renin-angiotensin system is well known that it plays an important role in the initiation and amplification of atherosclerosis that lead to cardiovascular disease. Angiotensin II is deeply involved in vasoconstriction, oxidative stress, inflammation, thrombosis, vascular remodeling, and sympathetic nerve activity. Many studies have documented the favorable effects of angiotensin converting enzyme inhibitor(ACE-I) and angiotensin receptor blocker(ARB) on cardiovascular disease in basic and clinical trials. Now accumulated evidences suggest ACE-I and ARB potentially prevent coronary plaque rapture, thrombosis and myocardial remodeling with acute coronary syndrome (ACS). ACS is occurred from plaque rupture on mild to moderate coronary atherosclerosis. Therefore, on treatment of ACS, it is important to prevent the plaque rupture and thrombosis by pharmacological intervention with ACE-I and ARB than coronary artery intervention which is down stream therapy for coronary artery stenosis.
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PMID:[Use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers in patients with acute coronary syndrome]. 1661 92

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

The NAD(P)H oxidase is an enzyme assembled at the cellular membrane able to produce superoxide anion from NADH or NAD(P)H (nicotinamide adenine dinucleotide phosphate). It is one of the main sources of superoxide anion in cardiovascular tissues and its role in a variety of cardiovascular disorders such as atherosclerosis, cardiac hypertrophy, and endothelial dysfunction was recently proposed. Although, many factors and receptors were shown to lead to the activation of the enzyme, particulary the type 1 angiotensin receptor, the pathways involved are still widely unknown. Despite the identification of factors such as c-Src and protein kinase C implicated in the acute activation of NAD(P)H oxidase, the signalling involved in the sustained activation of the enzyme is probably far more complex than was previously envisioned. In this review, we describe the role of endothelin-1 in NAD(P)H oxidase signalling after a sustained stimulation by angiotensin II. Since most pathologies caused by an NAD(P)H oxidase overactivation develop over a relatively long period of time, it is necessary to better understand the long-term signalling of the enzyme for the development or use of more specific therapeutic tools.
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PMID:The interrelation of the angiotensin and endothelin systems on the modulation of NAD(P)H oxidase. 1684 87

The endothelium is critically involved in modulating vascular tone through the release of vasodilator (mainly nitric oxide; NO) and vasoconstrictor agents. Under normal conditions the endothelium induces NO-mediated vasodilation, and opposes cell adhesion and thrombosis. Angiotensin II-induced generation of reactive oxygen species plays a key role in the pathophysiology of endothelial dysfunction by reducing NO bioavailability. Endothelial dysfunction is associated with several pathologic conditions, including hypertension and diabetes, and is characterized by altered vascular tone, inflammation, and thrombosis in the vascular wall. Inhibition of the renin-angiotensin-aldosterone system has induced beneficial effects on endothelial function in animals and humans. Angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and mineralocorticoid receptor antagonists have improved endothelial function in hypertension and diabetes, slowed the progression of atherosclerosis, and reduced the risk associated with cardiovascular disease.
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PMID:Inhibition of the renin angiotensin system: implications for the endothelium. 1687 78


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