Endothelial cell oxidative stress in diabetes: a key driver of cardiovascular complications?

2014 ◽  
Vol 42 (4) ◽  
pp. 928-933 ◽  
Author(s):  
Andrew Shaw ◽  
Mary K. Doherty ◽  
Nicola J. Mutch ◽  
Sandra M. MacRury ◽  
Ian L. Megson
Keyword(s):  
Endothelial Cells ◽  
Reactive Oxygen Species Generation ◽  
Specific Effect ◽  
Cardiovascular Complications ◽  
High Morbidity ◽  
Substantial Evidence ◽  
Hypo Glycaemia ◽  
Key Driver ◽  
Key Steps ◽  
The Impact

Atherothrombotic disease is a well-recognized complication of diabetes and is a major contributor to the high morbidity and mortality associated with diabetes. Although there is substantial evidence linking diabetes with cardiovascular disease, the specific effect of hyper- (or hypo-) glycaemia is less well understood. The present review focuses on the impact that glycaemic dysregulation has on respiratory function and ROS (reactive oxygen species) generation in the endothelial cells that are critical in preventing several key steps in the atherothrombotic process. Endothelial cells are particularly susceptible to ROS-mediated dysfunction not only because of reduced cell viability and increased senescence, but also because one of the major endothelium-derived factors that help to protect against atherosclerosis, nitric oxide, is rapidly deactivated by superoxide radicals.

scholarly journals Mechanosensation and Mechanotransduction by Lymphatic Endothelial Cells Act as Important Regulators of Lymphatic Development and Function

2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus
Keyword(s):  
Endothelial Cells ◽  
Endothelial Cell ◽  
Cell Fate ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Mechanical Forces ◽  
Lymphatic Endothelial Cells ◽  
Lymphatic Development ◽  
And Function ◽  
The Impact

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.

scholarly journals 231 Impact of Brachyspira hyodysentariae on intestinal function and integrity

2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 116-116
Author(s):  
Emma T Helm ◽  
Susanne J Lin ◽  
Nicholas Gabler ◽  
Eric R Burrough
Keyword(s):  
Ex Vivo ◽  
Potato Starch ◽  
Nutrient Digestibility ◽  
High Morbidity ◽  
Post Inoculation ◽  
Intestinal Function ◽  
Treatment Groups ◽  
Intestinal Integrity ◽  
Beet Pulp ◽  
The Impact

Abstract Swine dysentery (SD) induced by Brachyspira hyodysentariae (Bhyo) causes colitis and mucohemorrhagic diarrhea in grow-finish pigs, however little is known about the physiological changes that occur to the gastrointestinal tract during Bhyo infection. Thus, the objective of this study was to evaluate the impact of a Bhyo challenge on intestinal function and integrity of pigs fed two divergent diets. A total of 36 Bhyo negative gilts (24.3 ± 3.6 kg BW) were selected and assigned to one of three treatment groups (n=12 pigs/trt): 1) Bhyo negative, 20% DDGS diet (CON), 2) Bhyo challenged, 20% DDGS diet (DDGS), and 3) Bhyo challenged, 10% DDGS, 5% beet pulp and 5% resistant potato starch diet (RS). Pigs were fed diets 21 days prior to challenge and on days post inoculation (dpi) 0 and 1, pigs were inoculated with Bhyo or sham. Fecal samples were collected for ATTD and pigs were euthanized for colon collection within 72 hours of initial observation of clinical SD, or at the end of the study (dpi 10-16). Tissues were assessed for ex vivo measures of intestinal integrity and mitochondrial function. The challenge resulted in high morbidity, with 88% of DDGS and RS pigs developing clinical SD. Colon transepithelial resistance was increased in DDGS pigs compared with CON and RS pigs (P=0.005), and colon macromolecule permeability was reduced in both DDGS and RS pigs compared with CON pigs (P=0.006), likely due to mucoid discharge. Colonic mitochondrial oxygen consumption was not impacted by treatment (P >0.10). Further, ATTD of DM, OM, N, and GE were reduced in DDGS pigs compared with CON pigs (P< 0.001), whilst nutrient digestibility was not reduced in RS pigs. Taken together, these data show Bhyo does not appear to reduce ex vivo colonic integrity. Further, the RS diet may reduce severity of a Bhyo challenge.

scholarly journals Cognitive decline in patients with prostate cancer: study protocol of a prospective cohort, NEON-PC

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e043844
Author(s):  
Natalia Araujo ◽  
Samantha Morais ◽  
Ana Rute Costa ◽  
Raquel Braga ◽  
Ana Filipa Carneiro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cognitive Decline ◽  
Cognitive Performance ◽  
Androgen Deprivation Therapy ◽  
Survival Rates ◽  
Cardiovascular Complications ◽  
Androgen Deprivation ◽  
High Survival ◽  
The Impact

IntroductionProstate cancer is the most prevalent oncological disease among men in industrialised countries. Despite the high survival rates, treatments are often associated with adverse effects, including metabolic and cardiovascular complications, sexual dysfunction and, to a lesser extent, cognitive decline. This study was primarily designed to evaluate the trajectories of cognitive performance in patients with prostate cancer, and to quantify the impact of the disease and its treatments on the occurrence of cognitive decline.MethodsParticipants will be recruited from two main hospitals providing care to approximately half of the patients with prostate cancer in Northern Portugal (Portuguese Institute of Oncology of Porto and São João Hospital Centre), and will comprise a cohort of recently diagnosed patients with prostate cancer proposed for different treatment plans, including: (1) radical prostatectomy; (2) brachytherapy and/or radiotherapy; (3) radiotherapy in combination with androgen deprivation therapy and (4) androgen deprivation therapy (with or without chemotherapy). Recruitment began in February 2018 and is expected to continue until the first semester of 2021. Follow-up evaluations will be conducted at 1, 3, 5, 7 and 10 years. Sociodemographic, behavioural and clinical characteristics, anxiety and depression, health literacy, health status, quality of life, and sleep quality will be assessed. Blood pressure and anthropometrics will be measured, and a fasting blood sample will be collected. Participants’ cognitive performance will be evaluated before treatments and throughout follow-up (Montreal Cognitive Assessment and Cube Test as well as Brain on Track for remote monitoring). All participants suspected of cognitive impairment will undergo neuropsychological tests and clinical observation by a neurologist.Ethics and disseminationThe study was approved by the Ethics Committee of the hospitals involved. All participants will provide written informed consent, and study procedures will be developed to ensure data protection and confidentiality. Results will be disseminated through publication in peer-reviewed journals and presentation in scientific meetings.

scholarly journals Decomposition Analysis of the Evolution of the Local Energy System as a Tool to Assess the Effect of Local Actions: Methodology and Example of Malmö, Sweden

Energies ◽  
2021 ◽  
Vol 14 (2) ◽  
pp. 461
Author(s):  
Isabel Azevedo ◽  
Vítor Leal
Keyword(s):  
Local Level ◽  
Ghg Emissions ◽  
Decomposition Analysis ◽  
Specific Effect ◽  
Energy System ◽  
Local Energy ◽  
Total Change ◽  
The Impact ◽  
Change Mitigation

This paper proposes the use of decomposition analysis to assess the effect of local energy-related actions towards climate change mitigation, and thus improve policy evaluation and planning at the local level. The assessment of the impact of local actions has been a challenge, even from a strictly technical perspective. This happens because the total change observed is the result of multiple factors influencing local energy-related greenhouse gas (GHG) emissions, many of them not even influenced by local authorities. A methodology was developed, based on a recently developed decomposition model, that disaggregates the total observed changes in the local energy system into multiple causes/effects (including local socio-economic evolution, technology evolution, higher-level governance frame and local actions). The proposed methodology, including the quantification of the specific effect associated with local actions, is demonstrated with the case study of the municipality of Malmö (Sweden) in the timeframe between 1990 and 2015.

The Obesity Paradox in Emergency General Surgery Patients

2021 ◽  
pp. 000313482096852
Author(s):  
Sean R. Maloney ◽  
Caroline E. Reinke ◽  
Abdelrahman A. Nimeri ◽  
Sullivan A. Ayuso ◽  
A. Britton Christmas ◽  
...  
Keyword(s):  
General Surgery ◽  
Multivariable Analysis ◽  
Operative Management ◽  
Chronic Obstructive ◽  
High Morbidity ◽  
Emergency General Surgery ◽  
Common Procedure ◽  
Increased Risk ◽  
Social Security Death Index ◽  
The Impact

Operative management of emergency general surgery (EGS) diagnoses involves a range of procedures which can carry high morbidity and mortality. Little is known about the impact of obesity on patient outcomes. The aim of this study was to examine the association between body mass index (BMI) >30 kg/m2 and mortality for EGS patients. We hypothesized that obese patients would have increased mortality rates. A regional integrated health system EGS registry derived from The American Association for the Surgery of Trauma EGS ICD-9 codes was analyzed from January 2013 to October 2015. Patients were stratified into BMI categories based on WHO classifications. The primary outcome was 30-day mortality. Longer-term mortality with linkage to the Social Security Death Index was also examined. Univariate and multivariable analyses were performed. A total of 60 604 encounters were identified and 7183 (11.9%) underwent operative intervention. Patient characteristics include 53% women, mean age 58.2 ± 18.7 years, 64.2% >BMI 30 kg/m2, 30.2% with chronic obstructive pulmonary disease, 19% with congestive heart failure, and 31.1% with diabetes. The most common procedure was laparoscopic cholecystectomy (36.4%). Overall, 90-day mortality was 10.9%. In multivariable analysis, all classes of obesity were protective against mortality compared to normal BMI. Underweight patients had increased risk of inpatient (OR = 1.9, CI = 1.7-2.3), 30-day (OR = 1.9, CI = 1.7-2.1), 90-day (OR = 1.8, CI 1.6-2.0), 1-year (OR = 1.8, CI = 1.7-2.0), and 3-year mortality (OR = 1.7, CI = 1.6-1.9). When stratified by BMI, underweight EGS patients have the highest odds of death. Paradoxically, obesity appears protective against death, even when controlling for potentially confounding factors. Increased rates of nonoperative management in the obese population may impact these findings.

scholarly journals New Pathogenic Concepts and Therapeutic Approaches to Oxidative Stress in Chronic Kidney Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-21 ◽  
Author(s):  
José Pedraza-Chaverri ◽  
Laura G. Sánchez-Lozada ◽  
Horacio Osorio-Alonso ◽  
Edilia Tapia ◽  
Alexandra Scholze
Keyword(s):  
Oxidative Stress ◽  
Chronic Kidney Disease ◽  
Vitamin D ◽  
Kidney Disease ◽  
Cardiovascular Complications ◽  
Vitamin D Metabolism ◽  
Therapy Options ◽  
Mitochondrial Alterations ◽  
Inflammatory Processes ◽  
The Impact

In chronic kidney disease inflammatory processes and stimulation of immune cells result in overproduction of free radicals. In combination with a reduced antioxidant capacity this causes oxidative stress. This review focuses on current pathogenic concepts of oxidative stress for the decline of kidney function and development of cardiovascular complications. We discuss the impact of mitochondrial alterations and dysfunction, a pathogenic role for hyperuricemia, and disturbances of vitamin D metabolism and signal transduction. Recent antioxidant therapy options including the use of vitamin D and pharmacologic therapies for hyperuricemia are discussed. Finally, we review some new therapy options in diabetic nephropathy including antidiabetic agents (noninsulin dependent), plant antioxidants, and food components as alternative antioxidant therapies.

Modern approach to the treatment of arterial hypertension

2021 ◽  
pp. 28-34
Author(s):  
Dmitriy Sergeevich Kovalev
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Arterial Hypertension ◽  
Pathological Condition ◽  
Cardiovascular Complications ◽  
European Population ◽  
Modern Approach ◽  
Appropriate Treatment ◽  
Literary Sources ◽  
The Impact

Arterial hypertension (AH) refers to an increase in blood pressure above the level of 140/90 mm Hg; the risk of cardiovascular complications increases significantly with this pathological condition. Thus, arterial hypertension is an independent risk factor for the development of prediabetes / type 2 diabetes mellitus, heart failure, coronary heart disease, chronic kidney damage, and multifocal atherosclerosis. The frequency of arterial hypertension occurrence varies in different countries: in particular, it is from 23 to 36% for the European population, according to various literary sources. The main goal of treatment is to minimize the overall risk of developing cardiovascular complications. This involves the impact on all identified reversible risk factors, such as smoking and high cholesterol levels, and most importantly, appropriate treatment of concomitant diseases (diabetes mellitus, thyroid gland pathology, kidney disease, etc.), as well as the correction of high blood pressure.

Abstract 222: Dkk1 and Msx2-Wnt7b Signaling Reciprocally Regulate the Endothelial-Mesenchymal Transition in Aortic Endothelial Cells

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Su-Li Cheng ◽  
Jian-su Shao ◽  
Abraham Behrmann ◽  
Karen Krchma ◽  
Dwight A Towler
Keyword(s):  
Endothelial Cells ◽  
Mesenchymal Cell ◽  
Type I ◽  
Cuboidal Cell ◽  
Aortic Endothelial Cells ◽  
Mesenchymal Transition ◽  
Cell Responses ◽  
The Impact ◽  
Endothelial Mesenchymal Transition ◽  
Aortic Endothelial

Objective Endothelial cells (ECs) can undergo an endothelial-mesenchymal transition (EndMT) during tissue fibrosis. Wnt- and Msx2-regulated signals participate in arteriosclerotic calcification and fibrosis. We studied the impact of Wnt7, Msx2, and Dkk1 (Wnt7 antagonist) on EndMT in primary aortic endothelial cells (AoECs). Methods and Results Transduction of AoECs with vectors expressing Dkk1 suppressed EC differentiation and induced a mineralizing myofibroblast phenotype. Dkk1 suppressed claudin 5, PECAM, cadherin 5 (Cdh5), Tie1 and Tie2. Dkk1 converted the cuboidal cell monolayer into a spindle-shaped multilayer and inhibited EC cord formation. Myofibrogenic and osteogenic markers - e.g., SM22, type I collagen, Osx, Runx2, alkaline phosphatase – were upregulated by Dkk1 via activin-like kinase / Smad pathways. Dkk1 increased fibrosis and mineralization of AoECs cultured under osteogenic conditions - the opposite of mesenchymal cell responses. Msx2 and Wnt7b maintained the “cobblestone” morphology of differentiated ECs and promoted EC marker expression. Deleting EC Wnt7b with the Cdh5-Cre transgene in Wnt7b(fl/fl);LDLR-/- mice upregulated aortic osteogenic genes (Osx, Sox9, Runx2, Msx2) and nuclear pSmad1/5, and increased collagen accumulation. Conclusions Dkk1 enhances EndMT in AoECs, while Msx2-Wnt7 signals stabilize EC phenotype. EC responses to Dkk1, Wnt7b, and Msx2 are the opposite of mesenchymal cell responses, coupling EC phenotypic stability with osteofibrogenic predilection during arteriosclerosis.

Enhanced mtDNA repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death

2002 ◽  
Vol 283 (1) ◽  
pp. L205-L210 ◽  
Author(s):  
Allison W. Dobson ◽  
Valentina Grishko ◽  
Susan P. LeDoux ◽  
Mark R. Kelley ◽  
Glenn L. Wilson ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cell Death ◽  
Dna Repair ◽  
Trypan Blue Exclusion ◽  
Mt Dna ◽  
Repair Capacity ◽  
Mtdna Damage ◽  
Pulmonary Arterial ◽  
Selective Enhancement ◽  
The Impact

In rat cultured pulmonary arterial (PA), microvascular, and venous endothelial cells (ECs), the rate of mitochondrial (mt) DNA repair is predictive of the severity of xanthine oxidase (XO)-induced mtDNA damage and the sensitivity to XO-mediated cell death. To examine the importance of mtDNA damage and repair more directly, we determined the impact of mitochondrial overexpression of the DNA repair enzyme, Ogg1, on XO-induced mtDNA damage and cell death in PAECs. PAECs were transiently transfected with an Ogg1-mitochondrial targeting sequence construct. Mitochondria-selective overexpression of the transgene product was confirmed microscopically by the observation that immunoreactive Ogg1 colocalized with a mitochondria-specific tracer and, with an oligonucleotide cleavage assay, by a selective enhancement of mitochondrial Ogg1 activity. Overexpression of Ogg1 protected against both XO-induced mtDNA damage, determined by quantitative Southern analysis, and cell death as assessed by trypan blue exclusion and MTS assays. These findings show that mtDNA damage is a direct cause of cell death in XO-treated PAECs.

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