scholarly journals Targeting Endothelial Dysfunction in Vascular Complications Associated with Diabetes

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Arpeeta Sharma ◽  
Pascal N. Bernatchez ◽  
Judy B. de Haan
Keyword(s):  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Vascular Protection ◽  
Mortality And Morbidity ◽  
Improved Outcomes ◽  
Overwhelming Evidence ◽  
Novel Strategy ◽  
Endogenous Antioxidant ◽  
Key Events

Cardiovascular complications associated with diabetes remain a significant health issue in westernized societies. Overwhelming evidence from clinical and laboratory investigations have demonstrated that these cardiovascular complications are initiated by a dysfunctional vascular endothelium. Indeed, endothelial dysfunction is one of the key events that occur during diabetes, leading to the acceleration of cardiovascular mortality and morbidity. In a diabetic milieu, endothelial dysfunction occurs as a result of attenuated production of endothelial derived nitric oxide (EDNO) and augmented levels of reactive oxygen species (ROS). Thus, in this review, we discuss novel therapeutic targets that either upregulate EDNO production or increase antioxidant enzyme capacity in an effort to limit oxidative stress and restore endothelial function. In particular, endogenous signaling molecules that positively modulate EDNO synthesis and mimetics of endogenous antioxidant enzymes will be highlighted. Consequently, manipulation of these unique targets, either alone or in combination, may represent a novel strategy to confer vascular protection, with the ultimate goal of improved outcomes for diabetes-associated vascular complications.

scholarly journals Endothelial Dysfunction in Diabetes Mellitus: Possible Involvement of Endoplasmic Reticulum Stress?

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Basma Basha ◽  
Samson Mathews Samuel ◽  
Chris R. Triggle ◽  
Hong Ding
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Clinical Trials ◽  
Endoplasmic Reticulum ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Therapeutic Agents ◽  
Recent Past

The vascular complications of diabetes mellitus impose a huge burden on the management of this disease. The higher incidence of cardiovascular complications and the unfavorable prognosis among diabetic individuals who develop such complications have been correlated to the hyperglycemia-induced oxidative stress and associated endothelial dysfunction. Although antioxidants may be considered as effective therapeutic agents to relieve oxidative stress and protect the endothelium, recent clinical trials involving these agents have shown limited therapeutic efficacy in this regard. In the recent past experimental evidence suggest that endoplasmic reticulum (ER) stress in the endothelial cells might be an important contributor to diabetes-related vascular complications. The current paper contemplates the possibility of the involvement of ER stress in endothelial dysfunction and diabetes-associated vascular complications.

scholarly journals Suicidal Erythrocyte Death in Metabolic Syndrome

Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 154
Author(s):  
Ignazio Restivo ◽  
Alessandro Attanzio ◽  
Luisa Tesoriere ◽  
Mario Allegra
Keyword(s):  
Metabolic Syndrome ◽  
Cell Death ◽  
Endothelial Dysfunction ◽  
Cell Membrane ◽  
Clinical Evidence ◽  
Current Knowledge ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Inflammatory Milieu ◽  
Cardiometabolic Factors

Eryptosis is a coordinated, programmed cell death culminating with the disposal of cells without disruption of the cell membrane and the release of endocellular oxidative and pro-inflammatory milieu. While providing a convenient form of death for erythrocytes, dysregulated eryptosis may result in a series of detrimental and harmful pathological consequences highly related to the endothelial dysfunction (ED). Metabolic syndrome (MetS) is described as a cluster of cardiometabolic factors (hyperglycemia, dyslipidemia, hypertension and obesity) that increases the risk of cardiovascular complications such as those related to diabetes and atherosclerosis. In the light of the crucial role exerted by the eryptotic process in the ED, the focus of the present review is to report and discuss the involvement of eryptosis within MetS, where vascular complications are utterly relevant. Current knowledge on the mechanisms leading to eryptosis in MetS-related conditions (hyperglycemia, dyslipidemia, hypertension and obesity) will be analyzed. Moreover, clinical evidence supporting or proposing a role for eryptosis in the ED, associated to MetS cardiovascular complications, will be discussed.

scholarly journals The Use of Coenzyme Q10 in Cardiovascular Diseases

Antioxidants ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 755
Author(s):  
Yoana Rabanal-Ruiz ◽  
Emilio Llanos-González ◽  
Francisco J. Alcain
Keyword(s):  
Oxidative Stress ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular System ◽  
Contractile Function ◽  
Artery Bypass ◽  
Bypass Graft ◽  
No Bioavailability ◽  
Coq10 Supplementation ◽  
Endogenous Antioxidant

CoQ10 is an endogenous antioxidant produced in all cells that plays an essential role in energy metabolism and antioxidant protection. CoQ10 distribution is not uniform among different organs, and the highest concentration is observed in the heart, though its levels decrease with age. Advanced age is the major risk factor for cardiovascular disease and endothelial dysfunction triggered by oxidative stress that impairs mitochondrial bioenergetic and reduces NO bioavailability, thus affecting vasodilatation. The rationale of the use of CoQ10 in cardiovascular diseases is that the loss of contractile function due to an energy depletion status in the mitochondria and reduced levels of NO for vasodilatation has been associated with low endogenous CoQ10 levels. Clinical evidence shows that CoQ10 supplementation for prolonged periods is safe, well-tolerated and significantly increases the concentration of CoQ10 in plasma up to 3–5 µg/mL. CoQ10 supplementation reduces oxidative stress and mortality from cardiovascular causes and improves clinical outcome in patients undergoing coronary artery bypass graft surgery, prevents the accumulation of oxLDL in arteries, decreases vascular stiffness and hypertension, improves endothelial dysfunction by reducing the source of ROS in the vascular system and increases the NO levels for vasodilation.

Abstract 344: Endothelin-1 Overexpression Exaggerates Diabetes-induced Endothelial Dysfunction

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Noureddine IDRIS KHODJA ◽  
Muhammad Oneeb Rehman Mian ◽  
Tlili Barhoumi ◽  
Sofiane Ouerd ◽  
Jordan Gornitsky ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Fold Increase ◽  
Wild Type ◽  
No Donor ◽  
Meclofenamic Acid ◽  
Fibronectin Expression ◽  
Endothelium Dependent Relaxation

Objective: Vascular disease associated with endothelial dysfunction is a major cause of morbidity in patients with type-1 diabetes. Endothelin (ET)-1 plays a role in diabetes-induced vascular complications, since ET-1 type A receptor blockade reduces diabetes-induced vascular injury. However, whether ET-1 contributes to diabetes-induced endothelial dysfunction remains unproven. We hypothesized that vascular ET-1 overexpression will exaggerate diabetes-induced endothelial dysfunction. Methods: Diabetes was induced by streptozotocin treatment (STZ, 55 mg/kg/day, ip) for 5 days in 6-week-old male wild-type (WT) mice and in mice overexpressing ET-1 restricted to the endothelium (eET-1). Mice were studied 14 weeks later. Blood was collected to determine glucose. Mesenteric artery reactivity and remodeling were evaluated using pressurized myography and aortic fibronectin expression by immnunofluorescence. Results: STZ-induced diabetes was confirmed by a 3-fold increase in glycemia in WT and eET-1 ( P <0.001). Diabetes impaired endothelium-dependent relaxation (EDR) reponses to acetylcholine in WT (60.9±6.4% vs 83.9±3.4%, P <0.05) and eET-1 (48.6±5.1% vs 81.5±5.2%, P <0.001). EDR impairment was exaggerated in eET-1 compared to WT ( P <0.05). Meclofenamic acid, an inhibitor of cyclooxygenase, increased EDR in eET-1 compared to WT (78.4±9.4% vs 66.7±3.2%, P <0.01), which was not observed in diabetic mice. L-NAME, an inhibitor of nitric oxide (NO) synthase, completely blocked EDR in WT, eET-1 and diabetic WT, but not in diabetic eET-1 (4.1±1.6%, 6.4±5.7%, 2.2±4.6% and 26.6±4.6%, P <0.05). Apamin plus Tram34, inhibitors of endothelium-dependent hyperpolarization inhibited EDR in the four groups. Endothelium-independent relaxation to sodium nitroprusside, a NO donor, was similar in the four groups. Diabetes reduced media/lumen in WT (2.7±0.3 vs 3.6±0.3, P <0.05) and eET-1 (2.9±0.2 vs 3.8±0.3, P <0.05). Diabetes decreased aortic fibronectin expression in WT (94.0±11.0 vs. 151.9±21.8 RFU/μm 2 , P <0.05) and eET-1 (66.3±8.7 vs. 146.6±20.7 RFU/μm 2 , P <0.05). Conclusion: ET-1 contributes to alterations in several pathways mediating endothelium-dependent relaxation in type-1 diabetes, leading to exaggerated endothelial dysfunction.

scholarly journals The Role of Endothelial Dysfunction in the Pathogenesis of Vascular Complications of Diabetes Mellitus - A High Priority Area of Investigation

2015 ◽  
Vol 22 (1) ◽  
pp. 61-66 ◽  
Author(s):  
Rodica Teodora Străchinariu
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Vascular Complications ◽  
Noninvasive Methods ◽  
Cardiovascular Damage ◽  
Vasoactive Substances ◽  
Organ Systems ◽  
Increased Risk

Abstract Endothelium, the inner layer of the vasculature, represents the interface between blood and organ systems and it is active in the process of contraction and relaxation of vascular smooth muscle and in functions like secretion of vasoactive substances. Endothelial dysfunction is an important cause of cardiovascular disease. The function of the endothelium can be assessed by invasive and noninvasive methods. Endothelial cells produce vasoactive substances like endothelium derived relaxing factor, prostacyclin, nitric oxide, and endothelium derived hyperpolarizing factor. Diabetes mellitus is associated with an increased risk of cardiovascular diseases. Hyperglycemia leads to cardiovascular damage through different pathways, including the polyol and hexosamine pathways, generation of advanced glycation end products, and activation of protein kinase C. Together with hyperglycemia induced mitochondrial dysfunction and endoplasmic reticulum stress, all these can promote the accumulation of reactive oxygen species. The oxidative stress induced by hyperglycemia promotes endothelial dysfunction with an important role in micro and macro vascular disease. Insulin-resistance could be independently predictive of cardiovascular disease. Life style modification and pharmacotherapy could possibly ameliorate the effect of insulin resistance

scholarly journals The role of diabetes in the onset and development of endothelial dysfunction

2020 ◽  
Vol 66 (1) ◽  
pp. 47-55
Author(s):  
Era B. Popyhova ◽  
Tatiana V. Stepanova ◽  
Dar’ya D. Lagutina ◽  
Tatiana S. Kiriiazi ◽  
Alexey N. Ivanov
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Critical Role ◽  
Vascular Complications ◽  
Glycation End Products ◽  
Smooth Muscle Cell Migration ◽  
Basic Functions ◽  
Cell Migration And Proliferation ◽  
Radical Processes

The vascular endothelium performs many functions. It is a key regulator of vascular homeostasis, maintains a balance between vasodilation and vasoconstriction, inhibition and stimulation of smooth muscle cell migration and proliferation, fibrinolysis and thrombosis, and is involved to regulation of platelet adhesion and aggregation. Endothelial dysfunction (ED) plays the critical role in pathogenesis of diabetes mellitus (DM) vascular complications. The purpose of this review was to consider the mechanisms leading to the occurrence of ED in DM. The paper discusses current literature data concerning the role of hyperglycemia, oxidative stress, advanced glycation end products in endothelial alteration. A separate section is devoted to the particularities of the functioning of the antioxidant system and their significance in the development of ED in DM. The analysis of the literature allows to conclude that pathological activation of glucose utilization pathways causes damage of endothelial cells, which is accompanied by disorders of all their basic functions. Metabolic disorders in DM cause a pronounced imbalance of free radical processes and antioxidant defense, accompanied by oxidative stress of endotheliocytes, which contributes to the progression of ED and the development of vascular complications. Many aspects of multicomponent regulatory reactions in the pathogenesis of the development of ED in DM have not been sufficiently studied.

Abstract 357: Hepatic ERK2 Suppresses Endoplasmic Reticulum Stress, Leading to Protection from Oxidative Stress and Endothelial Dysfunction

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Takehiko Kujiraoka ◽  
Yasushi Satoh ◽  
Makoto Ayaori ◽  
Yasunaga Shiraishi ◽  
Yuko Arai-Nakaya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Endoplasmic Reticulum ◽  
Fatty Acid ◽  
Endothelial Dysfunction ◽  
Er Stress ◽  
Vascular Complications ◽  
Metabolic Remodeling ◽  
And Oxidative Stress

Background Insulin signaling comprises 2 major cascades, the IRS/PI3K/Akt and Ras/Raf/MEK/ERK pathways. Many studies on the tissue-specific effects of the former pathway had been conducted, however, the role of the latter cascade in tissue-specific insulin resistance had not been investigated. High glucose/fatty acid toxicity, inflammation and oxidative stress, all of which are associated with insulin resistance, can activate ERK. Liver plays a central role of metabolism and hepatosteatosis (HST) is associated with vascular diseases. The aim of this study is to elucidate the role of hepatic ERK2 in HST, metabolic remodeling and endothelial dysfunction. Methods Serum biomarkers of vascular complications in human were compared between subjects with and without HST diagnosed by echography for regular medical checkup. Next, we created liver-specific ERK2 knockout mice (LE2KO) and fed them with a high-fat/high-sucrose diet (HFHSD) for 20 weeks. The histological analysis, the expression of hepatic sarco/endoplasmic reticulum (ER) Ca 2+ -ATPase 2 (SERCA2) and glucose-tolerance/insulin-sensitivity (GT/IS) were tested. Vascular superoxide production and endothelial function were evaluated with dihydroethidium staining and isometric tension measurement of aorta. Results The presence of HST significantly increased HOMA-IR, an indicator of insulin resistance or atherosclerotic index in human. HFHSD-fed LE2KO revealed a marked exacerbation in HST and metabolic remodeling represented by the impairment of GT/IS, elevated serum free fatty acid and hyperhomocysteinemia without changes in body weight, blood pressure and serum cholesterol/triglyceride levels. In the HFHSD-fed LE2KO, mRNA and protein expressions of hepatic SERCA2 were significantly decreased, which resulted in hepatic ER stress. Induction of vascular superoxide production and remarkable endothelial dysfunction were also observed in them. Conclusions Hepatic ERK2 revealed the suppression of hepatic ER stress and HST in vivo , which resulted in protection from vascular oxidative stress and endothelial dysfunction. HST with hepatic ER stress can be a prominent risk of vascular complications by metabolic remodeling and oxidative stress in obese-related diseases.

Higher Cardiac Vagal Activity Predicts Lower Peripheral Resistance Six Years Later in European but not African Americans

2021 ◽  
Author(s):  
DeWayne P. Williams ◽  
Julian F. Thayer ◽  
James D. Halbert ◽  
Xiaoling Wang ◽  
Gaston Kapuku
Keyword(s):  
Cardiac Output ◽  
Peripheral Resistance ◽  
Cardiovascular Complications ◽  
Vagal Activity ◽  
Differential Impact ◽  
Full Sample ◽  
Mortality And Morbidity ◽  
European Americans ◽  
Lower Blood

African American (AA) individuals are at a greater risk for the development of cardiovascular complications, such as hypertension, compared to European Americans (EAs). Higher vagally mediated heart rate variability (HRV) is typically associated with lower blood pressure (BP) and total peripheral resistance (TPR). However, research has yet to examine the differential impact of HRV on longitudinal hemodynamic activity between AAs and EAs. We sought to rectify this in a sample of 385 normotensive youths (207 AAs, 178 EAs; mean age 23.16 ± 2.9 years). Individuals participated in two laboratory evaluations spanning approximately six years. Bio-impedance was used to assess HRV at time 1 and cardiac output at both time 1 and time 2. Mean arterial pressure (i.e., BP) was measured at both timepoints via an automated BP machine. TPR was calculated as MAP divided by cardiac output. Results showed AAs to have higher BP and higher TPR at time 2 compared to EAs, independent of several important covariates. Also, higher HRV at time 1 significantly predicted both lower TPR and BP at time 2 among EAs only; these associations were attenuated and not significant in AAs. HRV did not significantly predict cardiac output at time 2 in the full sample or split by ethnicity. Our findings highlight that AAs show TPR mediated long-term increases in BP irrespective of resting HRV, providing a physiological pathway linking AAs with a greater risk for mortality and morbidity from hypertension and potentially other cardiovascular disease.

Icariin Attenuates High Glucose-Induced Apoptosis, Oxidative Stress, and Inflammation in Human Umbilical Venous Endothelial Cells

Planta Medica ◽  
2019 ◽  
Vol 85 (06) ◽  
pp. 473-482 ◽  
Author(s):  
Si Sun ◽  
Le Liu ◽  
Xiaojun Tian ◽  
Yanghongyun Guo ◽  
Yingkang Cao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Glucose ◽  
Vascular Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Vascular Complications ◽  
Flavonoid Glycoside ◽  
Inflammatory Factors ◽  
Diabetic Vascular Complications ◽  
Induced Apoptosis

AbstractEndothelial dysfunction is closely associated with diabetic complications. Icariin, a flavonoid glycoside isolated from the Epimedium plant species, exhibits antidiabetic properties. However, its impact on endothelial function remains poorly understood, particularly under hyperglycemia. In this study, we investigated the potential protective effect of icariin on high glucose-induced detrimental effects on vascular endothelial cells. Human umbilical venous endothelial cells were incubated in media containing 5.5 mM glucose (normal glucose) or 25 mM glucose (high glucose) in the presence or absence of 50 µM icariin for 72 h. We found that high glucose markedly induced cell apoptosis, enhanced reactive oxygen species generation, and elevated expression levels of inflammatory factors and cell adhesion molecules, which were greatly subdued by icariin supplementation. In conclusion, icariin exerted a beneficial effect on high glucose-induced endothelial dysfunction. This new finding provides a promising strategy for future treatment of diabetic vascular complications.

scholarly journals Endothelial dysfunction: Mechanisms of development and therapeutic options

2006 ◽  
Vol 59 (7-8) ◽  
pp. 335-341 ◽  
Author(s):  
Srdjan Pesic ◽  
Miroslav Radenkovic ◽  
Leposava Grbovic
Keyword(s):  
Endothelial Dysfunction ◽  
Ace Inhibitors ◽  
Vascular Endothelial Cells ◽  
Beta Blockers ◽  
Phosphodiesterase Inhibitors ◽  
Initial Step ◽  
Endothelial Damage ◽  
Lipid Lowering ◽  
Organic Nitrates ◽  
Vascular Protection

Introduction. Vascular endothelial cells play a key role in cardiovascular regulation by producing a number of potent vasoactive agents, including the vasodilator molecule nitric oxide (NO) and the vasoconstrictor peptide endothelin (ET). Endothelial dysfunction. Endothelial dysfunction is recognized as the initial step in the atherosclerotic process. Impairment of NO synthesis, or increased inactivation of NO by superoxide radicals, may account for the increased peripheral vascular tone, as well as contribute to the clinical consequences of different pathophysiological conditions-which include vascular hypertrophy, increased platelet and monocyte adhesion to the endothelium, atherosclerosis, myocardial infarction and stroke. To date, most interventions attempting to improve endothelial dysfunction have targeted one or more of the numerous risk factors that can cause endothelial damage: hypertension (ACE inhibitors and calcium antagonists), hypercholesterolemia (lipid-lowering agents), cigarette smoking (cessation), sedentary lifestyle (increased physical activity), menopause (estrogen replacement therapy), and diabetes mellitus (control of metabolic abnormalities). Several pharmacologic agents have been suggested to achieve vascular protection through mechanisms that go beyond their primary therapeutic actions (ACE-and HMG-CoA reductase inhibitors). Beneficial changes to the endothelium might result from promotion of vasorelaxation, inhibition of vasoconstriction, reduction in the production of free radicals, or other mechanisms that protect the endothelium from injury. Conclusion. This study deals with the results of many experimental and clinical investigations. The possibility of using different classes of drugs was also established, including ACE inhibitors, Ca-antagonists, AT and endothelin receptor antagonists, direct activator of adenyl cyclase, statins, antioxidants, L-arginine, phosphodiesterase inhibitors, beta-blockers and organic nitrates. .

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