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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Accelerated atherosclerosis and microvascular complications are the leading causes of coronary heart disease, stroke, blindness, and end-stage renal failure, which could account for disabilities and high mortality rates in patients with diabetes. Recent clinical studies have substantiated the concept of "hyperglycemic memory" in the pathogenesis of cardiovascular disease (CVD) in diabetes. Indeed, the Diabetes Control and Complications Trial-Epidemiology of Diabetes Interventions and Complications (DCCT-EDIC) Research, has revealed that intensive therapy during the DCCT reduces the risk of cardiovascular events by about 50% in type 1 diabetic patients 11 years after the end of the trial. Among various biochemical pathways activated under diabetic conditions, 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 play an important role in CVD in diabetes. These observations suggest that the inhibition of AGEs formation may be a promising target for therapeutic intervention in diabetic vascular complications. Therefore, in this article, we review several agents with inhibitory effects on AGEs formation and their therapeutic implications in CVD in diabetes.
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PMID:Inhibitors of advanced glycation end products (AGEs): potential utility for the treatment of cardiovascular disease. 1846 20

Diabetic micro- and macroangiopathies are leading causes of acquired blindness, end-stage renal failure and accelerated atherosclerosis, which could account for disabilities and high mortality rates in patients with diabetes. Recent large landmark clinical studies have shown that intensive control of blood glucose or blood pressure (BP) reduces the risk for vascular complications in diabetes. However, the strict control of blood glucose or BP is often difficult to maintain, and current therapeutic options are far from satisfactory. Therefore, to develop novel therapeutic strategies that specifically target vascular complications in diabetes may be actually desired for most patients with diabetes. Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors with complex neurotrophic, neuroprotective, anti-angiogenic, anti-oxidative, and anti-inflammatory properties, any of which could potentially be exploited as a therapeutic option for the treatment of vascular complications in diabetes. This article summarizes the pathophysiological role of PEDF for vascular complication in diabetes and its potential therapeutic implication in this devastating disorder.
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PMID:Pigment epithelium-derived factor (PEDF): its potential therapeutic implication in diabetic vascular complications. 1899 13

The neovascular form of the age-related macular degeneration (AMD) causes most cases of severe blindness. Because vascular endothelial growth factor (VEGF) plays a leading role in this disorder, several inhibitors of this molecule are being used in its treatment. However, VEGF has important functions in vascular pathophysiology. It enhances the development of collateral vessels that may supply blood to areas whose arteries are severely affected by atherosclerotic lesions. Additionally, it may promote restoration of the damaged endothelium, a vessel layer that protects against the development of atherothrombosis, and it has hypotensive effects. In contrast, VEGF may stimulate the formation of microvessels inside the atherosclerotic plaque. These vessels may become disrupted and cause intraplaque hemorrhage, stimulating disease progression. VEGF also has a role in thrombus formation. The effects of anti-VEGF therapy may therefore compromise patient safety. When administered systemically to cancer patients, the main cardiovascular adverse effects of these compounds have been thrombosis, hemorrhage and hypertension. As patients with AMD constitute a high-risk population for cardiovascular events, the safety of new anti-VEGF therapies must be assessed. In this review we analyze the effects of VEGF on atherosclerosis and the cardiovascular safety of anti-VEGF therapies in AMD.
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PMID:Cardiovascular risk and antiangiogenic therapy for age-related macular degeneration. 1942 62

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. The formation and accumulation of advanced glycation end products (AGEs) have been known to progress at an accelerated rate in diabetes. Recent understanding of this process has confirmed that AGEs-their receptor RAGE system is implicated in the pathogenesis of diabetic vascular complication. Therefore, besides blood glucose and pressure control, the inhibition of the AGE-RAGE axis may be a novel therapeutic target for preventing vascular complications in diabetes. Recently, nifedipine, one of the most widely used Ca channel blockers, has been reported to exert anti-oxidative and anti-AGE-RAGE axis properties. The use of nifedipine, in addition to ensuring blood pressure control, may have beneficial effects in preventing cardiorenal vascular events in patients with diabetes.
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PMID:[Calcium antagonists: current and future applications based on new evidence. Calcium antagonists and diabetes]. 2004 37

Obesity and diabetes are becoming a pandemic in developing and industrialized countries. Based on the current criteria, 24.1 million Americans have diabetes, and another 57 million have prediabetes. The term prediabetes refers to people who have impaired fasting glucose (100-125 mg/dL), impaired glucose tolerance (2-hour postglucose load of 140-199 mg/dL), or both. Many persons with prediabetes already have microvascular disease consequences (eg, blindness, amputations, kidney failure) similar to those seen in patients with a diagnosis of diabetes. However, it is not established whether prediabetes should be considered a coronary heart disease risk equivalent. Whether dysglycemia is a surrogate for a more complex metabolic condition and/or directly increases cardiovascular disease (CVD) risk remains unclear. However, many studies have shown that hyperglycemia, through various mechanisms, can lead to premature atherosclerosis. In this regard, several diabetes prevention trials have shown that strategies that reduce the rate of conversion to diabetes can also modify CVD risk factors.
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PMID:Dysglycemia/prediabetes and cardiovascular risk factors. 2006 30

The essentiality of zinc was recognized 46 years ago. Zinc deficiency resulting in growth retardation, hypogonadism, immune dysfunction and cognitive impairment affects nearly 2 billion subjects in the developing world. High phytate content of the cereal proteins consumed in the developing world, results in decreased availability of zinc for absorption. Zinc therapy has been very successful and life saving measure in patients with acrodermatitis enteropathica and Wilson's disease. Beneficial therapeutic responses of zinc supplementation have been ovserved in acute diarrhea in children, chronic hepatitis C, shigellosis, leprosy, leishmaniasis, and common cold. Zinc supplementation was effective in decreasing incidences of infection in elderly and patients with sickle cell disease. Zinc supplementation was effective in preventing blindness in 25% of the elderly with dry type of age related macular degeneration. Zinc supplementation in the elderly decreased oxidative stress and decreased generation of inflammatory cytokines. Zinc is an intracellular signaling molecule in monocytes, dendritic cells and macrophages and it plays an important role in cell-mediated immune functions and oxidative stress. Zinc is also an anti-inflammatory agent. These unique properties of zinc may have significant therapeutic benefits in several diseases in humans. In many diseases concurrent zinc deficiency may complicate the clinical features, affect adversely immunological status, increase oxidative stress and increase generation of inflammatory cytokines. Oxidative stress and chronic inflammation may play important causative roles in many chronic diseases, including atherosclerosis, several malignancies, neurological disorders, and auto-immune diseases. It is therefore, important that status of zinc is assessed and zinc deficiency corrected in these chronic diseases. A controlled clinical trial of zinc supplementation in these disorders in order to document the preventive and therapeutic effects of zinc is warranted.
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PMID:Impact of the discovery of human zinc deficiency on health. 2015 May 99

Type 2 diabetes is an age-related disease associated with vascular pathologies, including severe blindness, renal failure, atherosclerosis, and stroke. Reactive oxygen species (ROS), especially mitochondrial ROS, play a key role in regulating the cellular redox status, and an overproduction of ROS may in part underlie the pathogenesis of diabetes and other age-related diseases. Cells have evolved endogenous defense mechanisms against sustained oxidative stress such as the redox-sensitive transcription factor nuclear factor E2-related factor 2 (Nrf2), which regulates antioxidant response element (ARE/electrophile response element)-mediated expression of detoxifying and antioxidant enzymes and the cystine/glutamate transporter involved in glutathione biosynthesis. We hypothesize that diminished Nrf2/ARE activity contributes to increased oxidative stress and mitochondrial dysfunction in the vasculature leading to endothelial dysfunction, insulin resistance, and abnormal angiogenesis observed in diabetes. Sustained hyperglycemia further exacerbates redox dysregulation, thereby providing a positive feedback loop for severe diabetic complications. This review focuses on the role that Nrf2/ARE-linked gene expression plays in regulating endothelial redox homeostasis in health and type 2 diabetes, highlighting recent evidence that Nrf2 may provide a therapeutic target for countering oxidative stress associated with vascular disease and aging.
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PMID:Impaired redox signaling and antioxidant gene expression in endothelial cells in diabetes: a role for mitochondria and the nuclear factor-E2-related factor 2-Kelch-like ECH-associated protein 1 defense pathway. 2052 45

Diabetic vascular complications are leading causes of acquired blindness, end-stage renal failure, a variety of neuropathies, and accelerated atherosclerosis, which may be involved in the disabilities and high mortality rates suffered by diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end-products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs (Glycer-AGEs), the predominant components of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, a growing body of evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) alters intracellular signaling, gene expression, and the release of pro-inflammatory molecules and elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic vascular complications. Therefore, the inhibition of TAGE formation, blockade of TAGE-RAGE interaction, and the suppression of RAGE expression or its downstream pathways are promising targets for therapeutic interventions against diabetic vascular complications. In this review, we discuss the pathophysiological role of the TAGE-RAGE-oxidative stress system and related therapeutic interventions for preventing the development and progression of diabetic vascular complications.
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PMID:Involvement of the toxic AGEs (TAGE)-RAGE system in the pathogenesis of diabetic vascular complications: a novel therapeutic strategy. 2058 71

Diabetic complications are a leading cause of acquired blindness, end-stage renal failure, and accelerated atherosclerosis, which are associated with the disabilities and high mortality rates seen in diabetic patients. Continuous hyperglycemia is involved in the pathogenesis of diabetic micro- and macrovascular complications via various metabolic pathways, and numerous hyperglycemia-induced metabolic and hemodynamic conditions exist, including increased generation of various types of advanced glycation end-products (AGEs). Recently, we demonstrated that glyceraldehyde-derived AGEs, the predominant structure of toxic AGEs (TAGE), play an important role in the pathogenesis of angiopathy in diabetic patients. Moreover, recent evidence suggests that the interaction of TAGE with the receptor for AGEs (RAGE) elicits oxidative stress generation in numerous types of cells, all of which may contribute to the pathological changes observed in diabetic complications. In this paper, we discuss the pathophysiological role of the TAGE-RAGE system in the development and progression of diabetic retinopathy.
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PMID:Involvement of TAGE-RAGE System in the Pathogenesis of Diabetic Retinopathy. 2065 47

Central retinal vein occlusion (CRVO) remains one of the most common retinal vascular disorders that may lead to blindness. The etiology is unknown, however, predisposing factors such as hypertension, diabetes, atherosclerosis and hypercoagulable states have all been described. Local ophthalmic illnesses such as open angle glaucoma, ocular trauma and orbital infections have also been suggested as causative. CRVO can be subdivided into two clinical types, ischemic and non-ischemic. The non-ischemic type comprises the milder form of the disease with partial venous obstruction and good visual outcome. Ischemic CRVO is the severe form and is associated with visual loss, because of nearly total retinal vein obstruction and poor perfusion to retina. In addition, patients with ischemic CRVO may end up with additional complications such as neovascular glaucoma that may lead to blindness. Over 90% of CRVO occurs in patients > 65 years. The presenting symptom is a sudden painless mono-ocular decrease in visual acuity which could result from macular edema, ischemia, or intraocular bleeding. Ophthalmoscopic examination reveals macular edema, retinal bleeding (more peripheral), tortuous vein dilatation and swollen disc. Current treatment modalities include systemic use of anticoagulation drugs, local treatments including laser, intravitreal injection of anti-vascular endothelial growth factor and surgery (vitrectomy). This review presents the current therapeutic modalities in CRVO.
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PMID:[Treatment modalities in central retinal vein occlusion]. 2081


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