The Experts below are selected from a list of 104118 Experts worldwide ranked by ideXlab platform
Hannele Yki-järvinen - One of the best experts on this subject based on the ideXlab platform.
-
Insulin resistance and Endothelial Dysfunction
Best practice & research. Clinical endocrinology & metabolism, 2003Co-Authors: Hannele Yki-järvinenAbstract:Insulin has multiple metabolic actions, including effects on blood vessels. Insulin normally increases blood flow by a mechanism which involves generation of nitric oxide (NO) via the arginine-NO pathway. Although insulin itself is a weak and physiologically unimportant vasodilatator, it appears to markedly potentiate endothelium-dependent vasodilatation. Therefore, anything that impairs insulin action in Endothelial cells can be expected to be associated with Endothelial Dysfunction, i.e. loss of NO bioactivity in the vessel wall. Consistent with the idea that insulin resistance and Endothelial Dysfunction frequently coexist, all insulin-resistant conditions examined to date have been associated with Endothelial Dysfunction. However, the latter can also be caused by factors other than insulin resistance-such as a high concentration of low-density lipoprotein (LDL) cholesterol. Therapies which reverse insulin resistance-such as exercise, insulin and inhibitors of the renin-angiotensin-aldosterone (RAA) axis-also reverse Endothelial Dysfunction, which may thus be an inherent feature of insulin resistance.
-
Endothelial Dysfunction in human diabetes
Current diabetes reports, 2002Co-Authors: Sari Mäkimattila, Hannele Yki-järvinenAbstract:In nondiabetic individuals, a poor response to an endothelium-dependent vasodilator in coronary vessels has been shown to increase the likelihood of a future cardiovascular event. Such prospective data are not as yet available in patients with type 1 or type 2 diabetes. However, consistent with the greatly increased cardiovascular risk in these patients, Endothelial Dysfunction has been almost universally found to characterize patients with type 2 diabetes particularly. Endothelial Dysfunction frequently coexists with features of insulin resistance, such as the presence of small dense low-density lipoprotein (LDL) particles even in nondiabetic individuals. This association is independent of obesity and other causes of Endothelial Dysfunction, such as LDL cholesterol, hypertension, and smoking. In patients with type 1 diabetes, Endothelial Dysfunction has been found in approximately half of the studies. In some but not all studies, Endothelial Dysfunction has been especially severe in patients with poor glycemic control. Reversal or amelioration of Endothelial Dysfunction has been documented by many commonly used therapeutic agents such as successful insulin therapy, fibrates, and angiotensin-converting enzyme inhibitors, but also with some but not all agents that act as antioxidants. Long-term studies addressing the prognostic significance of Endothelial Dysfunction and its reversal are urgently needed to determine whether measurement of Endothelial function could be used to identify individuals at risk better than can be done at present using classic risk factor assessment among patients with type 2 diabetes especially.
Paul M Vanhoutte - One of the best experts on this subject based on the ideXlab platform.
-
Macro- and microvascular Endothelial Dysfunction in diabetes.
Journal of diabetes, 2017Co-Authors: Yi Shi, Paul M VanhoutteAbstract:Endothelial cells, as well as their major products nitric oxide (NO) and prostacyclin, play a key role in the regulation of vascular homeostasis. Diabetes mellitus is an important risk factor for cardiovascular disease. Diabetes-induced Endothelial Dysfunction is a critical and initiating factor in the genesis of diabetic vascular complications. The present review focuses on both large blood vessels and the microvasculature. The Endothelial Dysfunction in diabetic macrovascular complications is characterized by reduced NO bioavailability, poorly compensated for by increased production of prostacyclin and/or endothelium-dependent hyperpolarizations, and increased production or action of endothelium-derived vasoconstrictors. The Endothelial Dysfunction of microvascular complications is primarily characterized by decreased release of NO, enhanced oxidative stress, increased production of inflammatory factors, abnormal angiogenesis, and impaired Endothelial repair. In addition, non-coding RNAs (microRNAs) have emerged as participating in numerous cellular processes. Thus, this reviews pays special attention to microRNAs and their modulatory role in diabetes-induced vascular Dysfunction. Some therapeutic strategies for preventing and restoring diabetic Endothelial Dysfunction are also highlighted.
-
Endothelial Dysfunction a multifaceted disorder the wiggers award lecture
American Journal of Physiology-heart and Circulatory Physiology, 2006Co-Authors: Michel Feletou, Paul M VanhoutteAbstract:Endothelial cells synthesize and release various factors that regulate angiogenesis, inflammatory responses, hemostasis, as well as vascular tone and permeability. Endothelial Dysfunction has been associated with a number of pathophysiological processes. Oxidative stress appears to be a common denominator underlying Endothelial Dysfunction in cardiovascular diseases. However, depending on the pathology, the vascular bed studied, the stimulant, and additional factors such as age, sex, salt intake, cholesterolemia, glycemia, and hyperhomocysteinemia, the mechanisms underlying the Endothelial Dysfunction can be markedly different. A reduced bioavailability of nitric oxide (NO), an alteration in the production of prostanoids, including prostacyclin, thromboxane A2, and/or isoprostanes, an impairment of endothelium-dependent hyperpolarization, as well as an increased release of endothelin-1, can individually or in association contribute to Endothelial Dysfunction. Therapeutic interventions do not necessarily restore a proper Endothelial function and, when they do, may improve only part of these variables.
-
Endothelial Dysfunction in diabetes
British Journal of Pharmacology, 2000Co-Authors: An S De Vriese, De V Van, N. H. Lameire, Tony J. Verbeuren, Paul M VanhoutteAbstract:Endothelial Dysfunction plays a key role in the pathogenesis of diabetic vascular disease. The endothelium controls the tone of the underlying vascular smooth muscle through the production of vasodilator mediators. The endothelium-derived relaxing factors (EDRF) comprise nitric oxide (NO), prostacyclin, and a still elusive endothelium-derived hyperpolarizing factor (EDHF). Impaired endothelium-dependent vasodilation has been demonstrated in various vascular beds of different animal models of diabetes and in humans with type 1 and 2 diabetes. Several mechanisms of Endothelial Dysfunction have been reported, including impaired signal transduction or substrate availibility, impaired release of EDRF, increased destruction of EDRF, enhanced release of endothelium-derived constricting factors and decreased sensitivity of the vascular smooth muscle to EDRF. The principal mediators of hyperglycaemia-induced Endothelial Dysfunction may be activation of protein kinase C, increased activity of the polyol pathway, non-enzymatic glycation and oxidative stress. Correction of these pathways, as well as administration of ACE inhibitors and folate, has been shown to improve endothelium-dependent vasodilation in diabetes. Since the mechanisms of Endothelial Dysfunction appear to differ according to the diabetic model and the vascular bed under study, it is important to select clinically relevant models for future research of Endothelial Dysfunction
Céline Demougeot - One of the best experts on this subject based on the ideXlab platform.
-
Microvascular Endothelial Dysfunction in rheumatoid arthritis
Nature Reviews Rheumatology, 2018Co-Authors: Romain Bordy, Perle Totoson, Clément Prati, Christine Marie, Daniel Wendling, Céline DemougeotAbstract:The systemic autoimmune disease rheumatoid arthritis (RA) is characterized by increased cardiovascular mortality and morbidity and is an independent cardiovascular risk factor. Cardiovascular diseases (CVDs) result from accelerated atherogenesis, which is a consequence of Endothelial Dysfunction in the early stages of the disease. Endothelial Dysfunction is a functional and reversible alteration of Endothelial cells and leads to a shift in the properties of the endothelium towards reduced vasodilation, a pro-inflammatory state, and proliferative and prothrombotic properties. In RA, Endothelial Dysfunction can occur in the large vessels (such as the conduit arteries) and in the small vessels of the microvasculature, which supply oxygen and nutrients to the tissue and control inflammation, repair and fluid exchange with the surrounding tissues. Growing evidence suggests that microvascular Endothelial Dysfunction contributes to CVD development, as it precedes and predicts the development of conduit artery atherosclerosis and associated risk factors. As such, numerous studies have investigated microvascular Endothelial Dysfunction in RA, including its link with disease activity, disease duration and inflammation, the effect of treatments on Endothelial function, and possible circulating biomarkers of microvascular Endothelial Dysfunction. Such findings could have important implications in the cardiovascular risk management of patients with RA.
-
Endothelial Dysfunction in joint disease.
Joint Bone Spine, 2014Co-Authors: Clément Prati, Céline Demougeot, Xavier Guillot, Marie Godfrin-valnet, Daniel WendlingAbstract:Abstract Inflammatory joint diseases and autoimmune diseases with joint manifestations are associated with premature and accelerated atherogenesis. Patients with rheumatoid arthritis (RA) have a 5- to 10-year decrease in life expectancy compared to the general population, and those exhibiting extraarticular manifestations have the greatest excess mortality. RA is now established as an independent cardiovascular risk factor. Complex interactions linking conventional cardiovascular risk factors, systemic inflammation, and vascular function may explain the increased cardiovascular risk among RA patients. Endothelial Dysfunction is now recognized as both the key step in early atherogenesis and a contributor to atheroma plaque progression at later stages. Endothelial Dysfunction is defined as impaired endothelium-dependent blood-vessel dilation in response to a stimulus. The underlying mechanisms remain speculative. Over the last decade, a role for Endothelial Dysfunction in the cardiovascular complications of inflammatory joint disease has been hypothesized and several maintenance drugs targeting this phenomenon have been tested, with promising results.
Yukihito Higashi - One of the best experts on this subject based on the ideXlab platform.
-
Diabetes and Endothelial Dysfunction
Diabetes and Aging-related Complications, 2017Co-Authors: Tatsuya Maruhashi, Yasuki Kihara, Yukihito HigashiAbstract:In patients with diabetes mellitus, Endothelial Dysfunction is the initial step in the process of atherosclerosis and plays an important role in the development of this condition, leading to diabetic vascular complications. Oxidative stress induced by hyperglycemia and acute glucose fluctuations are associated with Endothelial Dysfunction through inactivating nitric oxide (NO) by excess production of reactive oxygen species (ROS). Under the condition of insulin resistance, NO production is selectively impaired, whereas endothelin-1 (ET-1) secretion is preferentially activated in Endothelial cells, leading to Endothelial Dysfunction in obese or overweight diabetic patients. On the other hand, Endothelial Dysfunction might contribute to insulin resistance in skeletal muscle. Reduced NO production through oxidative stress and selective insulin resistance in Endothelial cells contributes to decreased glucose uptake by skeletal muscle due to a delayed increase in insulin concentration in the interstitium of the skeletal muscle. Therefore, insulin resistance is further exacerbated through a vicious cycle of Endothelial Dysfunction and reduced glucose uptake by skeletal muscle. From a clinical perspective, it is important to select an appropriate intervention that is effective in improving Endothelial Dysfunction for treatment of patients with diabetes mellitus.
-
Endothelial Dysfunction and hypertension in aging
Hypertension Research, 2012Co-Authors: Yukihito Higashi, Yasuki Kihara, Kensuke NomaAbstract:Hypertension is one of the common diseases in the elderly. The prevalence of hypertension markedly increases with advancing age. Both aging and hypertension have a critical role in cardiovascular and cerebrovascular complications. Although aging and hypertension, either independently or collectively, impair Endothelial function, aging and hypertension may have similar cascades for the pathogenesis and development of Endothelial Dysfunction. Nitric oxide (NO) has an important role in regulation of vascular tone. Decrease in NO bioavailability by Endothelial Dysfunction would lead to elevation of blood pressure. An imbalance of reduced production of NO or increased production of reactive oxygen species, mainly superoxide, may promote Endothelial Dysfunction. One possible mechanism by which the prevalence of hypertension is increased in relation to aging may be advancing Endothelial Dysfunction associated with aging through an increase in oxidative stress. In addition, Endothelial cell senescence is also involved in aging-related Endothelial Dysfunction. In this review, we focus on recent findings and interactions between Endothelial function, oxidative stress and hypertension in aging.
-
Renal Endothelial Dysfunction and hypertension.
Journal of diabetes and its complications, 2002Co-Authors: Yukihito Higashi, Kazuaki ChayamaAbstract:Patients with essential hypertension have an impaired endothelium-dependent vascular relaxation in the renal arteries. The possible mechanisms by which essential hypertension is associated with alterations in Endothelial function are decreased Endothelial nitric oxide (NO) synthase activity, decreased availability or deficiency of L-arginine, increased endogenous NO synthase inhibitor, inactivation of NO by superoxide anions, and increased vasoconstrictors. However, the precise mechanism is not known. In addition, we are now confronted with a difficult question. And the question is whether Endothelial Dysfunction is a cause or consequence of hypertension. We hypothesize that the initial Endothelial Dysfunction raises blood pressure, and the development of hypertension impairs much more Endothelial function, resulting in constituting the vicious cycle between Endothelial Dysfunction and hypertension. However, at the moment, it is impossible to answer this question with any certainty. Impairment of Endothelial function has been shown to play a critical role in the development and maintenance of hypertension. It is clinically important to select an appropriate intervention that is effective in improving Endothelial Dysfunction in patients with essential hypertension. Several investigators including us have demonstrated that certain interventions improve Endothelial Dysfunction of forearm and renal circulation in patients with essential hypertension: angiotensin-converting enzyme inhibitors; lifestyle modification: exercise, body weight reduction, and sodium reduction; estrogen replacement in postmenopausal women; and novel properties: vitamin C and tetrahydrobiopterine. In patients with essential hypertension, Endothelial function is impaired in several arteries. However, Endothelial Dysfunction in essential hypertension is reversible. We can restore Endothelial function in essential hypertensive patients.
Mark T. Kearney - One of the best experts on this subject based on the ideXlab platform.
-
Insulin resistance, lipotoxicity and Endothelial Dysfunction.
Biochimica et biophysica acta, 2009Co-Authors: Helen Imrie, Afroze Abbas, Mark T. KearneyAbstract:The number of people with the insulin-resistant conditions of type 2 diabetes mellitus (T2DM) and obesity has reached epidemic proportions worldwide. Eighty percent of people with T2DM will die from the complications of cardiovascular atherosclerosis. Insulin resistance is characterised by Endothelial Dysfunction, which is a pivotal step in the initiation/progression of atherosclerosis. A hallmark of Endothelial Dysfunction is an unfavourable imbalance between the bioavailability of the antiatherosclerotic signalling molecule nitric oxide (NO) and proatherosclerotic reactive oxygen species. In this review we discuss the mechanisms linking insulin resistance to Endothelial Dysfunction, with a particular emphasis on a potential role for a toxic effect of free fatty acids on Endothelial cell homeostasis.
