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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Atherosclerosis is a progressive human pathology that encompasses several stages of development. Endothelial dysfunction represents an early sign of lesion within the vasculature. A number of risk factors for atherosclerosis, including hyperlipidemia, diabetes, and hypertension, target the vascular endothelium by re-programming its transcriptome. These profound alterations taking place on the chromatin rely on the interplay between sequence specific transcription factors and the epigenetic machinery. The epigenetic machinery, in turn, tailor individual transcription events key to atherogenesis to intrinsic and extrinsic insults dictating the development of atherosclerotic lesions. This review summarizes our current understanding of the involvement of the epigenetic machinery in endothelial injury during atherogenesis.
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PMID:Transcriptional regulation of endothelial dysfunction in atherosclerosis: an epigenetic perspective. 2447 63

The vascular endothelium is a monolayer of cells that cover the interior of blood vessels and provide both structural and functional roles. The endothelium acts as a barrier, preventing leukocyte adhesion and aggregation, as well as controlling permeability to plasma components. Functionally, the endothelium affects vessel tone. Endothelial dysfunction is an imbalance between the chemical species which regulate vessel tone, thombroresistance, cellular proliferation and mitosis. It is the first step in atherosclerosis and is associated with coronary artery disease, peripheral artery disease, heart failure, hypertension, and hyperlipidemia. The first demonstration of endothelial dysfunction involved direct infusion of acetylcholine and quantitative coronary angiography. Acetylcholine binds to muscarinic receptors on the endothelial cell surface, leading to an increase of intracellular calcium and increased nitric oxide (NO) production. In subjects with an intact endothelium, vasodilation was observed while subjects with endothelial damage experienced paradoxical vasoconstriction. There exists a non-invasive, in vivo method for measuring endothelial function in peripheral arteries using high-resolution B-mode ultrasound. The endothelial function of peripheral arteries is closely related to coronary artery function. This technique measures the percent diameter change in the brachial artery during a period of reactive hyperemia following limb ischemia. This technique, known as endothelium-dependent, flow-mediated vasodilation (FMD) has value in clinical research settings. However, a number of physiological and technical issues can affect the accuracy of the results and appropriate guidelines for the technique have been published. Despite the guidelines, FMD remains heavily operator dependent and presents a steep learning curve. This article presents a standardized method for measuring FMD in the brachial artery on the upper arm and offers suggestions to reduce intra-operator variability.
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PMID:Ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery in clinical research. 2540 39

Postprandial lipemia has been associated with acute endothelial dysfunction. Endothelial dysfunction, in turn, is associated with increased arterial stiffness. However, the relationship between postprandial lipemia and acute changes in arterial stiffness has not been extensively investigated. Therefore, we conducted a pilot study on the effects of postprandial lipemia on arterial stiffness in 19 healthy young adults before and after consumption of a high-fat mixed meal. Arterial stiffness was assessed locally with echo-tracking carotid arterial strain (CAS) and globally with carotid-femoral pulse wave velocity (PWV). As assessed by these two benchmark parameters, arterial stiffness did not differ significantly postprandially. However, the arterial distension period (ADP) was significantly lower 2 hours after mixed meal ingestion. In addition, slopes of carotid artery area (CAA) curves were significantly steeper postprandially. Therefore, we concluded that ADP may be a more sensitive marker of arterial stiffness in healthy young adults when compared to PWV and CAS.
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PMID:Postprandial effects on arterial stiffness parameters in healthy young adults. 2606 82

Statin therapy targeting reduction of low-density lipoprotein cholesterol (LDL-C) decreases the risk of coronary heart disease (CHD) and all-cause mortality. However, a substantial number of cases of CHD are not prevented and residual risk factors remain unsettled. A high triglyceride (TG) level is considered to be an important and residual risk factor. Postprandial hyperlipidemia is a condition in which TG-rich chylomicron remnants are increased during the postprandial period and hypertriglycedemia is protracted. Postprandial hyperlipidemia evokes atherogenesis during the postprandial period. Several prospective studies have revealed that nonfasting serum TG levels predict the incidence of CHD. Values of TG, remnant lipoprotein cholesterol, and remnant lipoprotein TG after fat loading were significantly higher in diabetes patients with insulin resistance than in diabetes patients without insulin resistance. Endothelial dysfunction is an initial process of atherogenesis and it contributes to the pathogenesis of CHD. Postprandial hyperlipidemia (postprandial hypertriglyceridemia) is involved in the production of proinflammatory cytokines, recruitment of neutrophils, and generation of oxidative stress, resulting in endothelial dysfunction in healthy subjects, hypertriglyceridemic patients, or type 2 diabetic patients. Effective treatment has not been established till date. Ezetimibe or omega-3 fatty acids significantly decrease postprandial TG elevation and postprandial endothelial dysfunction. Ezetimibe or omega-3 fatty acids added to statin therapy reduce serum TG levels and result in good outcomes in patients with CHD. In conclusion, postprandial hyperlipidemia is an important and residual risk factor especially in patients with insulin resistance syndrome (metabolic syndrome) and diabetes mellitus. Further studies are needed to establish effective treatment.
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PMID:Postprandial hyperlipidemia as a potential residual risk factor. 2674 35

Nilotinib is an oral potent tyrosine kinase inhibitor that has diverse biological activities. However, its effects on hypercholesterolemia and associated disorders have not been studied yet. The present study explored the effect of nilotinib on atherosclerosis progression, endothelial dysfunction, and hyperlipidemia-associated hepatic injury in high-cholesterol (HC)-fed rabbits. Rabbits were classified into four groups: control, nilotinib, HC, and HC + nilotinib groups. Rabbits were fed either a regular diet or an HC-enriched diet for 8 weeks. By the end of the eighth week, blood and tissue samples were obtained for biochemical, histological, immunohistochemical, and in vitro analyses. Results indicated that the HC diet induced a significant elevation in the serum lipid parameters (triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol), lactate dehydrogenase, and nitric oxide content. Endothelial dysfunction was evident through the impairment of acetylcholine-induced relaxation of isolated aortas and the histopathological lesions of the aortic specimen. Moreover, HC significantly increased serum malondialdehyde. Liver damage was clear through increase in serum transaminases and alkaline phosphatase, and it was further supported by histopathological examination. HC increased the expression of platelet-derived growth factor receptor (PDGFR)-B in both aorta and liver tissues. Interestingly, nilotinib administration retarded atherosclerosis progression and attenuated all of the aforementioned parameters. These data suggest that nilotinib may counteract atherosclerosis development, vascular dysfunction, and hepatic damage in HC-fed rabbits through interfering with PDGF-B.
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PMID:Nilotinib attenuates endothelial dysfunction and liver damage in high-cholesterol-fed rabbits. 2794 Nov 69

Epidemiology studies and clinical trials show that omega-3 polyunsaturated fatty acids (n-3 PUFAs) can prevent atherosclerotic morbidity and evidence suggests this may be mediated by improving endothelial dysfunction. Endothelial dysfunction is characterized by reduced vasodilation and a pro-inflammatory, pro-thrombotic state, and is an early pathological event in the development of atherosclerosis. Flow-mediated dilation (FMD), a gold standard for assessing endothelial dysfunction, is a predictor of future cardiovascular events and coronary heart disease risk. Notably, risk factors for endothelial dysfunction include classic risk factors for atherosclerosis: Elevated lipids, diabetes, hypertension, elevated BMI, cigarette smoking, and metabolic syndrome. In this paper, we review the ability of n-3 PUFAs to improve endothelial dysfunction in individuals with classic risk factors for atherosclerosis, but lacking diagnosed atherosclerotic disease, with the goal of identifying those individuals that might gain the most vasoprotection from n-3 PUFA supplements. We include trials using eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or alpha-linolenic acid (ALA) alone, or EPA+DHA; and assessing endothelial function by FMD, forearm blood flow, or peripheral arterial tonometry. We found that n-3 PUFAs improved endothelial dysfunction in 16 of 17 studies in individuals with hyperlipidemia, elevated BMI, metabolic syndrome, or that smoked cigarettes, but only in 2 of 5 studies in diabetics. Further, these trials showed that use of EPA+DHA consistently improve endothelial dysfunction; ALA-enriched diets appear promising; but use of EPA or DHA alone requires further study. We conclude that individuals with hyperlipidemia, elevated BMI, metabolic syndrome, or that smoke could derive vaosprotective benefits from EPA+DHA supplementation.
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PMID:Omega-3 polyunsaturated fatty acids improve endothelial function in humans at risk for atherosclerosis: A review. 2880 71

Endothelial dysfunction is an initial pathophysiological mechanism of vascular damage and is further recognized as an independent predictor of negative prognosis in diabetes-induced micro- and macrovascular complications. Insight into the capability of zebrafish to model metabolic disease like obesity and type II diabetes has increased and new evidence on the induction of vascular pathologies in zebrafish through metabolic disease is available. Here, we raise the question, if zebrafish can be utilized to study the initial impairments of vascular complications in metabolic disorders. In this review, we focus on the advances made to develop models of obesity and type II diabetes in zebrafish, discuss the key points and characteristics of these models, while highlighting the available information linked to the development of endothelial dysfunction in zebrafish and man. We show that larval and adult zebrafish develop metabolic dysregulation in the settings of obesity and diabetes, exhibiting pathophysiological mechanisms, which mimic the human condition. The most important genes related to endothelial dysfunction are present in zebrafish and further display similar functions as in mammals. Several suggested contributors to endothelial dysfunction found in these models, namely hyperinsulinaemia, hyperglycaemia, hyperlipidaemia and hyperleptinaemia are highlighted and the available data from zebrafish are summarised. Many underlying processes of endothelial dysfunction in obesity and diabetes are fundamentally present in zebrafish and provide ground for the assumption, that zebrafish can develop endothelial dysfunction. Conservation of basic biological mechanisms is established for zebrafish, but focused investigation on the subject is now needed as validation and particularly more research is necessary to understand the differences between zebrafish and man. The available data demonstrate the relevance of zebrafish as a model for metabolic disease and their ability to become a proponent for the investigation of vascular damage in the settings of obesity and diabetes.
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PMID:Vascular Damage in Obesity and Diabetes: Highlighting Links Between Endothelial Dysfunction and Metabolic Disease in Zebrafish and Man. 3037 99

Atherosclerosis is the main cause of many cardiovascular diseases. Endothelial dysfunction is recognized as an early event in the development of atherosclerosis. Many drugs have been studied to mitigate hyperlipidemia-induced endothelial injury. Studies have demonstrated that neuropeptide substance P (SP) and its preferred receptor neurokinin receptor 1 (NK-1R) are involved in the pathological progression of cardiovascular disease. In this study, we show that aprepitant, a selective NK-1R antagonist, possesses beneficial effects that protect endothelial cells from oxidized low-density lipoprotein (ox-LDL)-induced inflammatory response and injury. Our data demonstrate that NK-1R is expressed in both aortic and vein-originated endothelial cells and that ox-LDL treatment induces NK-1R expression. Treatment with aprepitant suppresses induction of endothelial vascular adhesion molecule (VCAM-1 and E-selectin) and cytokine by ox-LDL. The presence of aprepitant mitigates adhesion of monocytes to endothelial cells and the reduction in eNOS/NO triggered by ox-LDL. Mechanistically, we demonstrate that aprepitant suppresses ERK5-KLF2 axis activation. Silencing of KLF2 abolishes the inhibitory role of aprepitant on ox-LDL-induced inflammatory response, suggesting that its action is dependent on KLF2. Collectively, our data support that aprepitant exerts an anti-inflammatory effect. Further research is required to investigate the therapeutic potential of aprepitant in vascular inflammation resulting from atherosclerosis.
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PMID:The neurokinin-1 receptor antagonist aprepitant ameliorates oxidized LDL-induced endothelial dysfunction via KLF2. 3057 49

Erectile dysfunction (ED) is a common disorder that affects the quality of life of many patients. It is prevalent in more than half of males aged over 60 years. Increasing evidence suggests that ED is predominantly a vascular disorder. Endothelial dysfunction seems to be the common pathological process causing ED. Many common risk factors for atherosclerosis such as diabetes, hypertension, smoking, obesity and hyperlipidaemia are prevalent in patients with ED and so management of these common cardiovascular risk factors can potentially prevent ED. Phosphodiesterase type 5 inhibitors provide short-term change of haemodynamic factors to help initiate and maintain penile erection. They have been shown to be an effective and safe treatment strategy for ED in patients with heart disease, including those with ischaemic heart disease and hypertension.
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PMID:Erectile Dysfunction and Ischaemic Heart Disease. 3069 53

The endothelium consists of a monolayer of Endothelial Cells (ECs) which form the inner cellular lining of veins, arteries, capillaries and lymphatic vessels. ECs interact with the blood and lymph. The endothelium fulfils functions such as vasodilatation, regulation of adhesion, infiltration of leukocytes, inhibition of platelet adhesion, vessel remodeling and lipoprotein metabolism. ECs synthesize and release compounds such as Nitric Oxide (NO), metabolites of arachidonic acid, Reactive Oxygen Species (ROS) and enzymes that degrade the extracellular matrix. Endothelial dysfunction represents a phenotype prone to atherogenesis and may be used as a marker of atherosclerotic risk. Such dysfunction includes impaired synthesis and availability of NO and an imbalance in the relative contribution of endothelialderived relaxing factors and contracting factors such as endothelin-1 and angiotensin. This dysfunction appears before the earliest anatomic evidence of atherosclerosis and could be an important initial step in further development of atherosclerosis. Endothelial dysfunction was historically treated with vitamin C supplementation and L-arginine supplementation. Short term improvement of the expression of adhesion molecule and endothelial function during antioxidant therapy has been observed. Statins are used in the treatment of hyperlipidaemia, a risk factor for cardiovascular disease. Future studies should focus on identifying the mechanisms involved in the beneficial effects of statins on the endothelium. This may help develop drugs specifically aimed at endothelial dysfunction.
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PMID:Endothelial Dysfunction in Dyslipidaemia: Molecular Mechanisms and Clinical Implications. 3148 Sep 95


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