Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Statins inhibit 3-hydroxy-methylglutaryl coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme for cholesterol synthesis, and share the common mechanism of lowering circulating levels of low-density lipoprotein cholesterol. Among various statins, atorvastatin is the most widely used statin for the treatment of hypercholesterolemia. Recent clinical trials show that atorvastatin reduces the risk of cardiovascular events and slows the progression of atherosclerosis in patients with coronary artery diseases. Further, intensive therapy with atorvastatin is also associated with an early clinical benefit in patients with acute coronary syndrome. These observations support the concept that beyond lipid-lowering effects of atorvastatin, that is, pleiotropic effects, could contribute at least in part to cardiovascular event reduction. Diabetic vascular complication is a leading cause of end-stage renal failure, acquired blindness, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. However, whether atorvastatin therapy decreases the risk for the development and progression of diabetic vascular complications and the way that it might achieve these effects are not fully elucidated. In this paper, we focus on diabetic vascular complications and review the efficacy and safety of atorvastatin in the treatment of these devastating disorders. We further discuss here the possible vasculoprotective properties of atorvastatin in patients with diabetes.
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PMID:Atorvastatin and diabetic vascular complications. 1661 Nov 35

Age-related macular degeneration (AMD) is the leading cause of irreversible blindness in Australia and other Western countries. As there is no cure for AMD, and treatments to stop its progression have met with limited success, there is an interest in identifying modifiable risk factors to prevent or slow disease progression. To date, smoking is the only proven modifiable risk factor for AMD. Other factors under study include (i) cardiovascular risk factors such as hypertension, body mass index, and atherosclerosis; and (ii) dietary risk factors including fat and antioxidant intake, but so far these studies have produced conflicting results. Dietary fat in relation to AMD has recently attracted media attention. Despite very limited work supporting an association between vegetable fat and AMD, widespread publicity advocating margarine as a cause of AMD and encouraging use of butter instead has caused confusion and anxiety among sufferers of AMD and the general public, as well as concern among health professionals. The antioxidant carotenoids--lutein and zeaxanthin--found in dark green or yellow vegetables exist in high concentrations in the macula and are hypothesised to play a protective role. Of nine controlled trials of supplementation with carotenoids and other antioxidants, three suggested that various combinations of antioxidants and carotenoids were protective. While a low-fat diet rich in dark green and yellow vegetables is advocated in general, any specific recommendations regarding certain fats or antioxidant supplementation and AMD are not based on consistent findings at this stage.
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PMID:Modifiable risk factors for age-related macular degeneration. 1664 46

Vascular complications are a leading cause of blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. There is a growing body of evidence that formation and accumulation of advanced glycation end products (AGEs) progress during normal aging, and at an extremely accelerated rate in diabetes, thus being involved in the pathogenesis of diabetic vascular complications. Furthermore, the interaction by AGEs of their receptor, RAGE, activates down-stream signaling and evokes inflammatory responses in vascular wall cells. Therefore, inhibition of AGE formation or blockade of the RAGE signaling may be a promising target for therapeutic intervention to prevent diabetic vascular complications. This review discusses the molecular mechanisms of diabetic retinopathy, especially focusing on the AGE-RAGE system. Several types of inhibitors of the AGE-RAGE system and their therapeutic implications are also reviewed here.
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PMID:Advanced glycation end products (AGEs) and their receptor (RAGE) system in diabetic retinopathy. 1671 66

Diabetic complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis. Chronic hyperglycemia is initially involved in the pathogenesis of diabetic micro- and macro-vascular complications via various metabolic derangements. High glucose increased production of various types of advanced glycation end-products (AGEs). Recently, we found that glyceraldehyde-derived AGEs (AGE-2) play an important role in the pathogenesis of angiopathy in diabetic patients. There is considerable interest in receptor for AGEs (RAGE) found on many cell types, particularly those affected in diabetes. Recent studies suggest that interaction of AGE-2 (predominantly structure of toxic AGEs; TAGE) with RAGE alters intracellular signaling, gene expression, release of pro-inflamatory molecules and production of reactive oxygen species (ROS) that contribute towards the pathology of diabetic complications. We propose three pathways for the in vivo formation of AGE-2 precursor, glyceraldehyde, such as i) glycolytic pathway, ii) polyol pathway, and iii) fructose metabolic pathway. Glyceraldehyde can be transported or can leak passively across the plasma membrane. It can react non-enzymatically with proteins to lead to accelerated formation of TAGE at both intracellularly and extracellularly. In this review, we discuss the molecular mechanisms of diabetic complications, especially focusing on toxic AGEs (TAGE) and their receptor (RAGE) system.
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PMID:TAGE (toxic AGEs) theory in diabetic complications. 1671 80

Recent decades have seen a significant increase in the incidence of diabetes mellitus. The number of individuals with diabetes is projected to reach 300 million by the year 2025. Diabetes is a leading cause of blindness, renal failure, lower limb amputation, and an independent risk factor for atherosclerotic cardiovascular disease (CVD)--a leading cause of death in Western society. Understanding the molecular and cellular mechanisms by which diabetes mellitus promotes atherosclerosis is essential to developing methods to treat and prevent diabetes-associated CVD. This review summarizes our current knowledge of the mechanisms by which diabetes may promote atherogenesis and specifically focuses on a novel pathway linking these 2 conditions. We hypothesize that the accumulation of intracellular glucosamine observed in conditions of chronic hyperglycaemia may promote atherogenesis via a mechanism involving dysregulated protein folding, activation of endoplasmic reticulum (ER) stress, and increased glycogen synthase kinase (GSK)-3 activity. The identification of this novel mechanism provides a promising hypothesis and multiple new targets for potential therapeutic intervention in the treatment of diabetes mellitus and accelerated atherosclerosis.
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PMID:Mechanisms linking diabetes mellitus to the development of atherosclerosis: a role for endoplasmic reticulum stress and glycogen synthase kinase-3. 1684 89

The incidence and prevalence of diabetes have reached epidemic proportions worldwide. The reasons for the pandemic are the sharp rise in obesity, decline in physical activity and the increase in life expectancy. There are some 400,000 people with diagnosed diabetes in Israel and they are at a markedly increased risk for cardiovascular disease, blindness, end-stage renal disease and lower limb amputation. To effectively lower this significantly increased burden of disease, a comprehensive multidisciplinary approach to chronic disease management is required. To facilitate such an approach, the Israel Diabetes Association published a guideline for the diagnosis, prevention and treatment of diabetes. The guideline, based on the ADA (American Diabetes Association) and IDF (International Diabetes Federation) guidelines, was approved by other national professional societies including hypertension, family practice, obesity, nephrology, atherosclerosis and internal medicine. The guidelines highlight the metabolic syndrome and prediabetic states, interventions for the prevention of diabetes, the new definitions of diabetes and impaired glucose metabolism and the newly defined targets for glucose, lipid, cholesterol and blood pressure control. In addition, the recommendations for periodic review and screening for complications are summarized. The need for patient education and empowerment are emphasized as is the need for the development and implementation of unique tools including computerized treatment flow-charts, prompts and quality measures, for the long term management of a complex metabolic disease.
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PMID:[The guidelines for the diagnosis prevention and treatment of type 2 diabetes mellitus--2005]. 1698 42

Diabetes mellitus (DM) is a major health problem worldwide, which affects 18.2 million individuals (6.3% of the population) in the United States. Currently, the prevalence of Type 1 DM in the United States is estimated to be 1,000,000 individuals, and 30,000 new cases are diagnosed each year. In addition to end-stage renal disease (ESRD), DM is associated with blindness, accelerated atherosclerosis, dyslipidemia, cardio- and cerebrovascular disease, amputation, poor quality of life, and overall lifespan reduction. It accounts for more than 160,000 deaths per year in the United States alone. In 2002, the annual national direct and indirect costs of Types 1 and 2 DM exceeded $130 billion, which included hospital and physician care, laboratory tests, pharmaceutical products, and patient workdays lost because of disability or premature death. Hyperglycemia alone or in concert with hypertension is the primary factor influencing the development of major diabetic complications. From 1990 to 2001, the number of existing ESRD cases to DM increased by more than 300%, while the rate per million populations increased from 167% to 491%. The number is expected to grow 10-fold by 2030 to 1.3 million accounting for 60% of ESRD population. To date, DM is the leading indication for transplantation and is the cause of ESRD in more than 40% of all transplant recipients each year.
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PMID:The long-term management of pancreas transplantation. 1706 Aug 46

Accelerated atherosclerosis and microvascular complications are perhaps the leading cause of coronary heart disease, blindness and renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Several mechanisms including endothelial cell damage, platelet activation and aggregation, hypercoagulability, and impaired fibrinolysis are involved in the pathogenesis of thrombogenic diathesis in diabetes. However, the underlying molecular mechanism is not fully elucidated. A recent clinical study, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that the reduction in the risk of progressive retinopathy and nephropathy resulting from intensive therapy in patients with type 1 diabetes persist for at least several years, despite increasing hyperglycemia. In addition, intensive therapy during the DCCT also reduced the risk of cardiovascular events by about 50 % in type 1 diabetic patients 11 years after the end of the trial. These clinical studies strongly suggest that so-called 'hyperglycemic memory' causes chronic abnormalities in diabetic vessels that are not easily reversed, even by subsequent, relatively good control of blood glucose. Among various biochemical pathways implicated in diabetic vascular complications, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. In this review, we discuss the role of AGEs in thrombogenic abnormalities in diabetes, especially focusing on the deleterious effects of these macroproteins on endothelial cell function, platelet activation and aggregation, coagulation and fibrinolytic systems.
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PMID:Advanced glycation end products (AGEs) and cardiovascular disease (CVD) in diabetes. 1763 Sep 50

Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Chronic hyperglycemia is essentially involved in the development and progression of diabetic micro- and macroangiopathy. Among various metabolic derangements implicated in the pathogenesis of diabetic vascular complication, advanced glycation end product (AGE) hypothesis is most compatible with the theory of 'hyperglycemic memory'. In this review, we discuss the molecular mechanisms of diabetic vascular complication, specially focusing on AGEs and their receptor (RAGE) system. Several types of AGE inhibitors and their therapeutic implications in this devastating disorder are also discussed here.
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PMID:Advanced glycation end products (AGEs) and diabetic vascular complications. 1822 May 86

Diabetic vascular complication is a leading cause of acquired blindness, end-stage renal failure, a variety of neuropathies and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Although several hyperglycemia-elicited metabolic and hemodynamic derangements have been implicated in the pathogenesis of diabetic vascular complication, the process of formation and accumulation of advanced glycation end products (AGEs) and their mode of action are most compatible with the theory 'hyperglycemic memory'. Further, there is a growing body of evidence that AGEs and their receptor (RAGE) axis is involved in the pathogenesis of diabetic vascular complication. Indeed, the engagement of RAGE with AGEs is shown to elicit oxidative stress generation and subsequently evoke inflammatory responses in various types of cells, thus playing an important role in the development and progression of diabetic micro- and macroangiopathy. These observations suggest that down-regulation of RAGE expression or blockade of the RAGE downstream signaling may be a promising target for therapeutic intervention in diabetic vascular complication. In this review, we discuss several types of agents that could potentially inhibit RAGE expression or its downstream pathways and their therapeutic implications in diabetic vascular complication.
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PMID:Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication. 1828 75


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