Xiaohong Ji, Xing Wang, Zhonghui Ling, Yan Lv, Wei Yu, Ruizhe Jia, Hongjuan Ding
OBJECTIVE: The present study was designed to investigate whether the novel peptide cysteine-based peptide (Cys-peptide) had protective effects on preeclamptic animal and cell models. METHODS: We investigated effects of Cys-peptide on (1) preeclamptic symptoms (e.g. hypertension, proteinuria, fetal growth restriction (FGR)) in preeclampia-like rat models induced by lipopolysaccharides (LPS), (2) TNFα-induced cytotoxicity of human umbilical vascular endothelial cells (HUVECs) and HTR-8 cells (an immortalised human trophoblast cell line), (3) endothelial dysfunction and injured angiogenesis, (4) migration and invasion of trophoblast cells induced by TNFα...
April 1, 2020: Life Sciences
Minghui Ou, Huidong Zhao, Guoxin Ji, Xin Zhao, Qian Zhang
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been identified previously in the pathogenesis of hypertension and some gestational diseases. However, the biological functions of MALAT1 in pregnancy-induced hypertension (PIH) are still poorly understood. Herein, we aim to explore the functional relevance of MALAT1 in PIH and to explain the potential underlying mechanisms. We found that the levels of ET-1 and MALAT1 were upregulated and that of miR-150-5p were downregulated in the serum of pregnant women with PIH and the aortic endothelial cells (ECs) of reduced uterine perfusion pressure (RUPP)-induced rat models...
April 4, 2020: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
N B Chesnokova, T A Pavlenko, O V Beznos, A V Grigoryev
The endothelin system (ES) plays a complex role in the pathogenesis of various eye diseases as a local regulator of vascular tone as well as many other physiological processes. Components of ES - endothelins and their receptors - can be found nearly in all cellular structures of the eye, their concentration increases in the presence of many eye diseases. In glaucoma, ES is involved in the mechanisms of eye hypertension by influencing the secretion and outflow of aqueous humor. The increase of endothelin level leads to the decrease of perfusion pressure, hypoxia, astrocyte proliferation, increase of density and rigidity of lamina cribrosa, apoptosis of neural cells, and has a profibrogenic effect...
2020: Vestnik Oftalmologii
Yufeng Lu, Qingsheng Yu, Wanshou Guo, Yangquan Hao, Wei Sun, Liming Cheng
BACKGROUND: The pathogenesis of glucocorticoid (GC)-induced osteonecrosis (ON) of the femoral head remains unclear. Recent research has suggested that it is closely associated with injured bone microvascular endothelial cells (BMECs). However, few studies have used BMECs to perform research pertaining ON of the femoral head. OBJECTIVES: The objective of this study was to investigate the functional changes of BMECs treated with a GC and to detect the changes in related genes using microarrays...
March 2020: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
Diane Nzelu, Dan Dumitrascu-Biris, Theodoros Karampitsakos, Kypros K Nicolaides, Nikos A Kametas
INTRODUCTION: Chronic hypertension complicates 1-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-a (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11+0 to 13+6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia to those who did not and normotensive controls, and second, to evaluate the performance of these biomarkers in the prediction of preeclampsia...
April 1, 2020: Acta Obstetricia et Gynecologica Scandinavica
Xin Zhao, Jian Dou, Jinglin Cao, Yang Wang, Qingjun Gao, Qiang Zeng, Wenpeng Liu, Baowang Liu, Ziqiang Cui, Liang Teng, Junhong Zhang, Caiyan Zhao
The present study aimed to identify novel diagnostic differentially expressed microRNAs (miRNAs/miRs) in order to understand the molecular mechanisms underlying hepatocellular carcinoma. The expression data of miRNA and mRNA were downloaded for differential expression analysis. Optimal diagnostic differentially expressed miRNA biomarkers were identified via a random forest algorithm. Classification models were established to distinguish patients with hepatocellular carcinoma and normal individuals. A regulatory network between optimal diagnostic differentially expressed miRNA and differentially expressed mRNAs was then constructed...
March 19, 2020: Oncology Reports
Brianna Dufek, Daniel T Meehan, Duane Delimont, Gina Samuelson, Jacob Madison, Xiourui Shi, Flint Boettcher, Vincent Trosky, Michael Anne Gratton, Dominic Cosgrove
In 129 Sv autosomal Alport mice, the strial capillary basement membranes (SCBMs) progressively thicken between 5 and 9 weeks of age resulting in a hypoxic microenvironment with metabolic stress and induction of pro-inflammatory cytokines and chemokines. These events occur concomitant with a drop in endocochlear potential and a susceptibility to noise-induced hearing loss under conditions that do not permanently affect age/strain-matched littermates. Here we aimed to gain an understanding of events that occur before the onset of SCBM thickening...
March 18, 2020: Hearing Research
Mona A Said
Diabetes mellitus (DM) is associated with micro- and macrovascular complications and increased cardiovascular risk. Vitamin D deficiency is the most common nutrient deficiency in the world. This study aimed to examine the effects of diabetes on the endothelial function and the role of vitamin D supplementation. Male Wistar rats ( n  = 30) were randomly assigned to three groups; control untreated, diabetic untreated, and diabetic groups treated with vitamin D at a dose of 12.5 μg/kg body weight, dissolved in 0...
April 1, 2020: Archives of Physiology and Biochemistry
Lauren G Douma, Kristen Solocinski, Sarah H Masten, Dominique H Barral, Sarah J Barilovits, Lauren A Jeffers, Kareme D Alder, Ravi Patel, Charles S Wingo, Kevin D Brown, Brian D Cain, Michelle L Gumz
Endothelin-1 (ET-1) is a peptide hormone that functions as a vasoconstrictor in the vasculature, whereas in the collecting duct of the kidney it exerts blood pressure-lowering effects via natriuretic actions. Aberrant ET-1 signaling is associated with several pathological states including hypertension and chronic kidney disease. ET-1 expression is regulated largely through transcriptional control of the gene that encodes ET-1, EDN1 . Here we report a long, non-coding RNA (lncRNA) that appears to be antisense to the EDN1 gene, called EDN1-AS ...
2020: Frontiers in Physiology
Yajun Zheng, Xian Wang, Yongliang Zhuang, Yan Li, Panqi Shi, Hailong Tian, Xiaotian Li, Xing Chen
Naked oat globulin was hydrolyzed by alcalase, flavourzyme, pepsin, and trypsin in sequence. The hydrolysates (NOGH) were purified using gel chromatography, reversed-phase high performance liquid chromatography (RP-HPLC). Finally, fraction D7d with the highest ACE-inhibitory was subjected to liquid chromatography-mass spectrometry analysis and 14 peptides were identified. Of which, peptide SSYYPFK (890.4 Da) was chose to synthesize based on in silico analysis. The SSYYPFK demonstrated high ACE-inhibitory activity (IC50 : 91...
March 27, 2020: Journal of Food Science
Maryana Abrahamovych, Orest Abrahamovych, Oksana Fayura, Solomiya Tolopko
BACKGROUND: Liver is one of the first organs to be exposed to reactive oxygen species (ROS). But the data about the levels of redox homeostasis parameters in the patients with liver cirrhosis (LC) are contradictory. We hypothesized that the levels of malondialdehide and catalase should change in accordance with the LC severity causing the endothelial dysfunction. METHODS: In a randomized way with the preliminary startification by the presence of LC 81 patients and 20 healthy volunteers were examined...
March 24, 2020: Minerva Gastroenterologica e Dietologica
Caroline Kinnear, Rahul Agrawal, Caitlin Loo, Aric Pahnke, Deivid Carvalho Rodrigues, Tadeo Thompson, Oyediran Akinrinade, Samad Ahadian, Fred Keeley, Milica Radisic, Seema Mital, James Ellis
OBJECTIVE: Elastin gene deletion or mutation leads to arterial stenoses due to vascular smooth muscle cell (SMC) proliferation. Human induced pluripotent stem cells-derived SMCs can model the elastin insufficiency phenotype in vitro but show only partial rescue with rapamycin. Our objective was to identify drug candidates with superior efficacy in rescuing the SMC phenotype in elastin insufficiency patients. Approach and Results: SMCs generated from induced pluripotent stem cells from 5 elastin insufficiency patients with severe recurrent vascular stenoses (3 Williams syndrome and 2 elastin mutations) were phenotypically immature, hyperproliferative, poorly responsive to endothelin, and exerted reduced tension in 3-dimensional smooth muscle biowires...
March 26, 2020: Arteriosclerosis, Thrombosis, and Vascular Biology
Warisara Parichatikanond, Theerut Luangmonkong, Supachoke Mangmool, Hitoshi Kurose
Transforming growth factor-β (TGF-β) is a common mediator of cancer progression and fibrosis. Fibrosis can be a significant pathology in multiple organs, including the heart. In this review, we explain how inhibitors of TGF-β signaling can work as antifibrotic therapy. After cardiac injury, profibrotic mediators such as TGF-β, angiotensin II, and endothelin-1 simultaneously activate cardiac fibroblasts, resulting in fibroblast proliferation and migration, deposition of extracellular matrix proteins, and myofibroblast differentiation, which ultimately lead to the development of cardiac fibrosis...
2020: Frontiers in Cardiovascular Medicine
Raghda Ramadan, Els Vromans, Dornatien Chuo Anang, Ines Goetschalckx, Delphine Hoorelbeke, Elke Decrock, Sarah Baatout, Luc Leybaert, An Aerts
Background: Emerging evidence indicates an excess risk of late occurring cardiovascular diseases, especially atherosclerosis, after thoracic cancer radiotherapy. Ionizing radiation (IR) induces cellular effects which may induce endothelial cell dysfunction, an early marker for atherosclerosis. In addition, intercellular communication through channels composed of transmembrane connexin proteins (Cxs), i.e. Gap junctions (direct cell-cell coupling) and hemichannels (paracrine release/uptake pathway) can modulate radiation-induced responses and therefore the atherosclerotic process...
2020: Frontiers in Pharmacology
Devang M Patel, Madhura Bose, Mark E Cooper
The major clinical associations with the progression of diabetic kidney disease (DKD) are glycemic control and systemic hypertension. Recent studies have continued to emphasize vasoactive hormone pathways including aldosterone and endothelin which suggest a key role for vasoconstrictor pathways in promoting renal damage in diabetes. The role of glucose per se remains difficult to define in DKD but appears to involve key intermediates including reactive oxygen species (ROS) and dicarbonyls such as methylglyoxal which activate intracellular pathways to promote fibrosis and inflammation in the kidney...
March 23, 2020: International Journal of Molecular Sciences
Angela C Zeigler, Anders R Nelson, Anirudha S Chandrabhatla, Olga Brazhkina, Jeffrey W Holmes, Jeffrey J Saucerman
The fibroblast is a key mediator of wound healing in the heart and other organs, yet how it integrates multiple time-dependent paracrine signals to control extracellular matrix synthesis has been difficult to study in vivo. Here, we extended a computational model to simulate the dynamics of fibroblast signaling and fibrosis after myocardial infarction (MI) in response to time-dependent data for nine paracrine stimuli. This computational model was validated against dynamic collagen expression and collagen area fraction data from post-infarction rat hearts...
March 21, 2020: Matrix Biology: Journal of the International Society for Matrix Biology
Lukas Bütikofer, Pierre A Varisco, O Distler, O Kowal-Bielecka, Y Allanore, G Riemekasten, P M Villiger, S Adler
OBJECTIVES: To investigate the effect of ACE inhibitors (ACEi) on the incidence of scleroderma renal crisis (SRC) when given prior to SRC in the prospectively collected cohort from the European Scleroderma Trial and Research Group (EUSTAR). METHODS: SSc patients without prior SRC and at least one follow-up visit were included and analyzed regarding SRC, arterial hypertension, and medication focusing on antihypertensive medication and glucocorticoids (GC). RESULTS: Out of 14,524 patients in the database, we identified 7648 patients with at least one follow-up...
March 24, 2020: Arthritis Research & Therapy
Isabel Y Buchsbaum, Pavel Kielkowski, Grazia Giorgio, Adam C O'Neill, Rossella Di Giaimo, Christina Kyrousi, Shahryar Khattak, Stephan A Sieber, Stephen P Robertson, Silvia Cappello
During embryonic development, excitatory projection neurons migrate in the cerebral cortex giving rise to organised layers. Periventricular heterotopia (PH) is a group of aetiologically heterogeneous disorders in which a subpopulation of newborn projection neurons fails to initiate their radial migration to the cortex, ultimately resulting in bands or nodules of grey matter lining the lateral ventricles. Although a number of genes have been implicated in its cause, currently they only satisfactorily explain the pathogenesis of the condition for 50% of patients...
March 24, 2020: EMBO Reports
Deviana Soraya Riu, Isharyah Sunarno, Efendi Lukas, Ellen T Wewengkang, Rizki Amalia
OBJECTIVE: This study aimed to evaluate the effect of aspirin and pravastatin compared with aspirin on endothelin-1 levels, and the pregnancy outcome in pregnant women high risk for preeclampsia. METHODS: It was a randomized clinical trial (RCT) analysis with block permutation. The sample divided into two groups. Group A as control has given aspirin 80mg and group B as an intervention group given aspirin 80mg plus pravastatin 20mg twice daily until 35 weeks gestation...
March 2020: Enfermería Clínica
Meena Halaka, Zuhaila A Hired, Grace E Rutledge, Carly M Hedgepath, Michael P Anderson, Haley St John, Jessica M Do, Parth R Majmudar, Caleb Walker, Asma Alawawdeh, Hannah M Stephen, Caleb C Reagor, Jeanette Adereti, Kiara Jamison, Katherine P Iglesias, Khadija Z Kirmani, Rebecca E Conway
The endothelins and their receptors are best known for their regulation of the vascular system. Their widespread expression in epithelial cells and their overexpression in some tumors has prompted investigation into their ability to regulate cancer progression. In this study, we assessed the mRNA expression of the major endothelin B receptor gene (EDNRB) isoforms and found differences in both mRNA and protein expression in normal breast cells and breast cancer cell lines. Knocking down the EDNRB gene in breast cancer cells altered invasiveness toward endothelin 3 (ET3), and we observed EDNRB isoform-specific regulation of breast cancer cell invasion and cell signaling, as well as isoform- and subtype-specific differences in breast cancer patient survival...
2020: Journal of Cancer
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