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Endothelial dysfunction

Young-Mee Kim, Seock-Won Youn, Varadarajan Sudhahar, Archita Das, Reyhaan Chandhri, Henar Cuervo Grajal, Junghun Kweon, Silvia Leanhart, Lianying He, Peter T Toth, Jan Kitajewski, Jalees Rehman, Yisang Yoon, Jaehyung Cho, Tohru Fukai, Masuko Ushio-Fukai
Mitochondrial dynamics are tightly controlled by fusion and fission, and their dysregulation and excess reactive oxygen species (ROS) contribute to endothelial cell (EC) dysfunction. How redox signals regulate coupling between mitochondrial dynamics and endothelial (dys)function remains unknown. Here, we identify protein disulfide isomerase A1 (PDIA1) as a thiol reductase for the mitochondrial fission protein Drp1. A biotin-labeled Cys-OH trapping probe and rescue experiments reveal that PDIA1 depletion in ECs induces sulfenylation of Drp1 at Cys644 , promoting mitochondrial fragmentation and ROS elevation without inducing ER stress, which drives EC senescence...
June 19, 2018: Cell Reports
Yu Liu, Samuel I Bloom, Anthony J Donato
In the United States and other westernized nations, cardiovascular diseases (CVDs) are the leading cause of death in adults over 65 years of age. Large artery stiffness and endothelial dysfunction are increased with age and age-associated arterial dysfunction is an important antecedent of CVDs. One age-associated change that may contribute to vascular dysfunction and CVD risk is an increase in the number of resident senescence cells in the vasculature. Senescent cells display a pro-oxidant, pro-inflammatory phenotype known as the senescence associated secretory phenotype (SASP)...
June 20, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Sandra López-Domènech, Celia Bañuls, Noelia Díaz-Morales, Irene Escribano-López, Carlos Morillas, Silvia Veses, Samuel Orden, Ángeles Álvarez, Víctor Manuel Víctor, Antonio Hernández-Mijares, Milagros Rocha
BACKGROUND: To evaluate the relationship between leukocyte-endothelial cell interactions and oxidative stress parameters in non-diabetic patients with different grades of obesity. MATERIAL AND METHODS: For this cross-sectional study, two hundred and twenty-five subjects were recruited from January 1, 2014 to December 31, 2016 and divided into groups according to BMI (<30 kg/m2 , 30-40 kg/m2 and >40 kg/m²). We determined clinical parameters, systemic inflammatory markers, soluble cellular adhesion molecules, leukocyte-endothelium cell interactions - rolling flux, velocity and adhesion - oxidative stress parameters - total ROS, total superoxide, glutathione - and mitochondrial membrane potential in PMNs...
June 20, 2018: European Journal of Clinical Investigation
Yusuf Koçluk, Burcu Kasım, Emine Alyamaç Sukgen, Ayşe Burcu
PURPOSE: To evaluate the complications and clinical results of Descemet membrane endothelial keratoplasty (DMEK) in patients with endothelial failure that occurred during the learning curve of a surgeon. METHODS: Fifty eyes of 50 patients with DMEK and ≥6 months of follow-up were included. The patients were divided into the first 25 (group 1) and the second 25 (group 2) procedures performed by the surgeon. Best corrected visual acuity (BCVA), central corneal thickness (CCT), unfolding time of the Descemet membrane (DM) graft, and intraoperative and postoperative complications were compared between groups...
June 2018: Arquivos Brasileiros de Oftalmologia
Bandana Shrestha, Priya K Prasai, Amir M Kaskas, Ankur Khanna, Vijay Letchuman, Sunjay Letchuman, J Steven Alexander, A Wayne Orr, Matthew D Woolard, Christopher B Pattillo
OBJECTIVE: Oxidative stress is a central event linked with endothelial dysfunction and inflammation in several vascular pathologies, marked by over-production of ROS and concomitant decreases in antioxidants e.g. GSH. Here we distinguish endothelial oxidative stress regulation and associated functional disparities in the two main vascular conduits, (arteries and veins) following decreases in GSH. METHODS: MAECs and VCECs were used as models of arterial and venular endothelium, respectively and BSO (0-100μM) was used to indirectly increase cellular oxidative stress...
June 20, 2018: Microcirculation: the Official Journal of the Microcirculatory Society, Inc
Yu-Chen Wang, An-Sheng Lee, Long-Sheng Lu, Liang-Yin Ke, Wei-Yu Chen, Jian-Wen Dong, Jonathan Lu, Zhenping Chen, Chih-Sheng Chu, Hua-Chen Chan, Taha Y Kuzan, Ming-Hsien Tsai, Wen-Li Hsu, Richard A F Dixon, Tatsuya Sawamura, Kuan-Cheng Chang, Chu-Huang Chen
Dysregulation of plasma lipids is associated with age-related cardiovascular diseases. L5, the most electronegative subfraction of chromatographically resolved low-density lipoprotein (LDL), induces endothelial dysfunction, whereas the least electronegative subfraction, L1, does not. In this study, we examined the effects of L5 on endothelial senescence and its underlying mechanisms. C57B6/J mice were intravenously injected with L5 or L1 (2 mg kg-1  day-1 ) from human plasma. After 4 weeks, nuclear γH2AX deposition and senescence-associated β-galactosidase staining indicative of DNA damage and premature senescence, respectively, were increased in the aortic endothelium of L5-treated but not L1-treated mice...
June 19, 2018: Aging Cell
Isaac B Rhea, Guilherme H Oliveira
PURPOSE OF REVIEW: With the continuing development of newer targeted therapies in oncology, it is necessary to understand their potential cardiovascular side effects. In this review, we discuss the association of novel targeted agents and left ventricular systolic dysfunction. RECENT FINDINGS: Within the last 5 years, multiple new agents have been developed to target specific cancer pathways and found to have off-targeted cardiotoxicity. The most recent example is the recognition of myocarditis caused by immune checkpoint inhibitors...
June 19, 2018: Current Treatment Options in Cardiovascular Medicine
Kirin Tan, Aaron H J Withers, Swee T Tan, Tinte Itinteang
The pathogenesis of Dupuytren's disease (DD) remains unclear although there is increasing evidence supporting the role of stem cells in this and other fibrotic conditions. This review examines the role of DD tissue-associated embryonic stem cells (ESCs) and mesenchymal stem cells (MSCs), and circulating fibrocytes and circulating MSCs, in the biology of DD. It is exciting to infer that dysfunction of an upstream ESC-like population within the affected tissue leads to the downstream development and proliferation of aberrant myofibroblasts through a putative MSC intermediate...
May 2018: Plastic and Reconstructive Surgery. Global Open
Maurizio Benucci, Francesca Bandinelli, Arianna Damiani, Francesca Li Gobbi, Maria Infantino, Valentina Grossi, Mariangela Manfredi
Background: Rheumatoid arthritis patients are exposed to a high risk of cardiovascular morbidity and mortality even in the early phases of the disease. Methods: We evaluated carotid common carotid intimal media thickness (ccIMT) intimal thickness and brachial flow-mediated dilation (FMD) of 45 rheumatoid arthritis patients without known cardiovascular risk factors or heart disease on a stable dose of prednisone 5.2±1.2 mg/day and Methotrexate 11.5±2.1 mg at baseline (T0) and after 12 months (T1) of treatment with Abatacept 125 mg/week...
2018: Journal of Inflammation Research
Jie Liu, Wang Wang, Lei Wang, Shihao Chen, Bo Tian, Kewu Huang, Chris J Corrigan, Sun Ying, Wei Wang, Chen Wang
IL-33 may play a role in the vascular remodelling of hypoxic pulmonary hypertension (PH) but the precise mechanisms are still unclear. We hypothesized that hypoxia promotes expression of IL-33 and its receptor ST2 on vascular endothelial cells, which in turn leads to dysfunction of vascular endothelial cells and smooth muscle cells contributing to PH. Immunohistochemistry showed that immunoreactivity for IL-33 and ST2 was significantly increased in lung tissue of murine model of hypoxia-induced PH (HPH) and of subjects with bronchiectasis-PH...
June 16, 2018: EBioMedicine
Shilpa Sharma, Puja K Mehta, Reza Arsanjani, Tara Sedlak, Zachary Hobel, Chrisandra Shufelt, Erika Jones, Paul Kligfield, David Mortara, Michael Laks, Marcio Diniz, C Noel Bairey Merz
BACKGROUND: The utility of exercise-induced ST-segment depression for diagnosing ischemic heart disease (IHD) in women is unclear. HYPOTHESIS: Based on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex-ECG) ST-depression in the absence of obstructive CAD, so-called "false positive" results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex-ECG...
June 19, 2018: Clinical Cardiology
Abrar Al-Mahmood Siddiquee, P Ganesan Adaikan, Lang Chu Lau, Baharudin Bin Said, Mark Chong, Jerry Chan, Swee Hin Teoh
AIM: To investigate the effect of intracavernous injection of human umbilical cord blood derived endothelial colony forming cells (HUCB ECFCs) on erectile dysfunction (ED) in Zucker Diabetic Fatty (ZDF) rat model. METHODS: Erectile function was assessed by cavernous nerve electrostimulation in ZDF rats aged 20-28 weeks. Following confirmation of severe ED at the age of 28 weeks, 21 ZDF rats were randomly assigned to three experimental groups: 1 million ECFCs, 2 million ECFCs, and phosphate buffered saline (PBS)...
June 16, 2018: Life Sciences
Tamas Csipo, Gabor A Fulop, Agnes Lipecz, Stefano Tarantini, Tamas Kiss, Priya Balasubramanian, Anna Csiszar, Zoltan Ungvari, Andriy Yabluchanskiy
Obesity is one of the major risk factors for cardiovascular diseases and its prevalence is increasing in all age groups, with the biggest impact observed in middle-aged and older adults. A critical mechanism by which obesity promotes vascular pathologies in these patients involves impairment of endothelial function. While endothelial dysfunction in large vessels promotes atherogenesis, obesity-induced microvascular endothelial dysfunction impairs organ perfusion and thereby is causally related to the pathogenesis of ischemic heart disease, chronic kidney disease, intermittent claudication, exercise intolerance, and exacerbates cognitive decline in aging...
June 18, 2018: GeroScience
Benjamin D Gastfriend, Sean P Palecek, Eric V Shusta
The blood-brain barrier (BBB) regulates the transport of ions, nutrients, and metabolites to help maintain proper brain function. This restrictive interface formed by brain microvascular endothelial cells excludes the majority of small and large molecule drugs from entering the brain, and blood-brain barrier dysfunction is a signature of many neurological diseases. Thus, in vitro models of the BBB based on brain endothelial cells have been developed to facilitate screening drugs for BBB permeability. However, while brain endothelial cells form the main interface, they work in concert with other brain-resident cells such as neural progenitor cells, pericytes, astrocytes, and neurons to form the neurovascular unit (NVU)...
March 2018: Current Opinion in Biomedical Engineering
Jing-Rong Lin, Yan-Jun Zheng, Ze-Bei Zhang, Wei-Li Shen, Xiao-Dong Li, Tong Wei, Cheng-Chao Ruan, Xiao-Hui Chen, Ding-Liang Zhu, Ping-Jin Gao
Endothelial-to-mesenchymal transition (EndoMT) has recently emerged as a potentially important contributor in promoting fibrosis in chronic kidney disease. However, little is known about the role and molecular basis of its involvement in hypertensive renal injury. Here, we aim to determine the role of SIRT (sirtuin) 3 on EndoMT in hypertensive renal injury and to explore its underlying mechanisms. We found that SIRT3 expression was significantly reduced in Ang II (angiotensin II)-induced hypertensive model, accompanied with induction of EndoMT and increased reactive oxygen species and renal fibrosis...
June 18, 2018: Hypertension
Norma C Serrano, Elizabeth Guio-Mahecha, Doris Cristina Quintero-Lesmes, Silvia Becerra-Bayona, María C Paez, Mónica Beltran, Víctor M Herrera, Lydia J Leon, David Williams, Juan P Casas
BACKGROUND AND AIMS: Pre-eclampsia constitutes a leading cause of maternal and perinatal morbidity and mortality. Pre-eclampsia susceptibility is believed to be associated with altered lipid profiles and abnormal lipid metabolism via lipid peroxidation that leads to endothelial dysfunction. The goal of this study was to evaluate the association of maternal blood lipid and apolipoprotein levels with pre-eclampsia in a large-scale study. METHODS: Using data from a large case-control study (1366 cases of pre-eclampsia and 1741 normotensive controls), the association between the distributions of eight lipid fractions and pre-eclampsia risk was evaluated using adjusted logistic regression models...
June 4, 2018: Atherosclerosis
Ayşe Ağbaş, Nur Canpolat, Salim Çalışkan, Alev Yılmaz, Hakan Ekmekçi, Mark Mayes, Helen Aitkenhead, Franz Schaefer, Lale Sever, Rukshana Shroff
Randomized trials in adults have shown reduced all-cause and cardiovascular mortality on hemodiafiltration (HDF) compared to high-flux hemodialysis (HD), but the mechanisms leading to improved outcomes are not clear. We studied biomarkers of inflammation, oxidative stress, anti-oxidant capacity and endothelial dysfunction in 22 children (13 female, age 8-15 years). All children received HD for at least 3 months, and were then switched to HDF, keeping all dialysis related parameters and dialysis time constant...
2018: PloS One
Kashmira Rajendra Hajare, Priya Patil, Jyoti Bansode
Idiopathic systemic capillary leak syndrome (ISCLS) is a very rare life-threatening disorder characterized by recurrent episodes of hypotension, hemoconcentration, and hypoalbuminemia. It is caused by transient endothelial dysfunction, leading to plasma leakage from intravascular to interstitial space. Here, we report a case of ISCLS with recurrent episodes of capillary leak which required a long-term prophylaxis with beta-2 adrenergic receptor agonist and theophylline. Although ISCLS is the rare entity, associated morbidity and mortality require physician's awareness to provide timely therapy...
May 2018: Indian Journal of Critical Care Medicine
Chin Theng Ng, Lai Yen Fong, Yoke Keong Yong, Muhammad Nazrul Hakim, Zuraini Ahmad
Endothelial barrier dysfunction leads to increased endothelial permeability and is an early step in the development of vascular inflammatory diseases such as atherosclerosis. Interferon-γ (IFN-γ), a proinflammatory cytokine, is known to cause increased endothelial permeability. However, the mechanisms by which IFN-γ disrupts the endothelial barrier have not been clarified. This study aimed to investigate how IFN-γ impairs the endothelial barrier integrity by specifically examining the roles of caldesmon, adherens junctions (AJs) and p38 mitogen-activated protein (MAP) kinase in IFN-γ-induced endothelial barrier dysfunction...
June 14, 2018: Cytokine
Paulien Vinke, Suzanne M Jansen, Renger F Witkamp, Klaske van Norren
Pulmonary arterial hypertension (PAH) is a progressive disease primarily affecting the pulmonary vasculature and heart. PAH patients suffer from exercise intolerance and fatigue, negatively affecting their quality of life. This review summarizes current insights in the pathophysiological mechanisms underlying PAH. It zooms in on the potential involvement of nutritional status and micronutrient deficiencies on PAH exercise intolerance and fatigue, also summarizing the potential benefits of exercise and nutritional interventions...
June 16, 2018: Heart Failure Reviews
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