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Endothelial dysfunction

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https://www.readbyqxmd.com/read/28822917/coexistence-of-aberrant-hematopoietic-and-stromal-elements-in-myelodysplastic-syndromes
#1
Salar Abbas, Archana Kini, Vivi M Srivastava, Marie Therese M, Sukesh C Nair, Aby Abraham, Vikram Mathews, Biju George, Sanjay Kumar, Aparna Venkatraman, Alok Srivastava
Myelodysplastic syndromes (MDS) are a group of clonal hematopoietic disorders related to hematopoietic stem and progenitor cell dysfunction. Several studies have shown the role of the bone marrow microenvironment in regulating hematopoietic stem, and progenitor function and their individual abnormalities have been associated with disease pathogenesis. In this study, we simultaneously evaluated hematopoietic stem cells (HSC), hematopoietic stem progenitor cells (HSPCs) and different stromal elements in a cohort of patients with MDS-refractory cytopenia with multilineage dysplasia (RCMD)...
August 9, 2017: Blood Cells, Molecules & Diseases
https://www.readbyqxmd.com/read/28822809/inhibition-of-soluble-epoxide-hydrolase-lowers-portal-hypertension-in-cirrhotic-rats-by-ameliorating-endothelial-dysfunction-and-liver-fibrosis
#2
Wensheng Deng, Yiming Zhu, Jiayun Lin, Lei Zheng, Chihao Zhang, Meng Luo
Epoxyeicostrienoic acids (EETs) are arachidonic acid derived meditators which are catalyzed by soluble epoxide hydrolase (sEH) to less active dihydroeicostrienoics acids (DHETS). The aim of our study is to investigate the effects of sEH inhibition on hepatic and systemic hemodynamics, hepatic endothelial dysfunction, and hepatic fibrosis in CCl4 cirrhotic rats. The sEH inhibitor,trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB) was administered to stabilize hepatic EETs by gavage at a dose of 1mg/kg/d...
August 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28822761/down-regulation-of-vascular-ppar-%C3%AE-contributes-to-endothelial-dysfunction-in-high-fat-diet-induced-obese-mice-exposed-to-chronic-intermittent-hypoxia
#3
Yanan Zhang, Chunlian Zhang, Haiou Li, Jingdong Hou
Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is associated with endothelial dysfunction. The prevalence of OSA is linked to an epidemic of obesity. CIH has recently been reported to cause endothelial dysfunction in diet-induced obese animals by exaggerating oxidative stress and inflammation, but the underlying mechanism remains unclear. PPAR-γ, a ligand-inducible transcription factor that exerts anti-oxidant and anti-inflammatory effects, is down-regulated in the peripheral tissues in diet-induce obesity...
August 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28821815/epac1-deficient-mice-have-bleeding-phenotype-and-thrombocytes-with-decreased-gpib%C3%AE-expression
#4
Gyrid Nygaard, Lars Herfindal, Kathrine S Asrud, Ronja Bjørnstad, Reidun K Kopperud, Eystein Oveland, Frode S Berven, Lene Myhren, Erling A Hoivik, Turid Helen Felli Lunde, Marit Bakke, Stein O Døskeland, Frode Selheim
Epac1 (Exchange protein directly activated by cAMP 1) limits fluid loss from the circulation by tightening the endothelial barrier. We show here that Epac1(-/-) mice, but not Epac2(-/-) mice, have prolonged bleeding time, suggesting that Epac1 may limit fluid loss also by restraining bleeding. The Epac1(-/-) mice had deficient in vitro secondary hemostasis. Quantitative comprehensive proteomics analysis revealed that Epac1(-/-) mouse platelets (thrombocytes) had unbalanced expression of key components of the glycoprotein Ib-IX-V (GPIb-IX-V) complex, with decrease of GP1bβ and no change of GP1bα...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28820443/omega-3-polyunsaturated-fatty-acids-improve-endothelial-dysfunction-in-chronic-renal-failure-role-of-enos-activation-and-of-oxidative-stress
#5
Michela Zanetti, Gianluca Gortan Cappellari, Davide Barbetta, Annamaria Semolic, Rocco Barazzoni
BACKGROUND: Endothelial dysfunction is a key vascular alteration in chronic kidney disease (CKD). Omega 3 (n-3) polyunsaturated fatty acids (PUFA) reduce vascular oxidative stress and inflammation. We investigated whether n-3 PUFA could reverse endothelial dysfunction in CKD by improving endothelial nitric oxide synthase (eNOS) function and oxidative stress. METHODS: 5/6 nephrectomized male Wistar rats (CKD; n = 10) and sham operated animals (SHAM; n = 10) were treated for 6 weeks with standard diet...
August 18, 2017: Nutrients
https://www.readbyqxmd.com/read/28820409/-the-role-of-angiogenic-factors-in-the-diagnostics-of-pregnancy-complicated-with-preeclampsia
#6
I Tagiyeva, S Aliyeva, S Bagirova, N Shamsadinskaya, K Agaeva
The pathophysiology of preeclampsia remains largely unknown. It has been hypothesized that placental ischemia is an early event, leading to placental production of a soluble factor or factors that cause maternal endothelial dysfunction, resulting in the clinical findings of hypertension, proteinuria, and edema. Here, we confirm that placental soluble fms-like tyrosine kinase 1 (sFlt1), an antagonist of vascular growth factor (VEGF) and placental growth factor (PIGF), is upregulated in preeclampsia, leading to increased systemic levels of sFlt1...
July 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28820397/long-term-feeding-with-bioactive-tripeptides-in-aged-hypertensive-and-normotensive-rats-special-focus-on-blood-pressure-and-bradykinin-induced-vascular-reactivity
#7
A Siltari, J Roivanen, R Korpela, H Vapaatalo
Bradykinin is the main player of the kallikrein-kinin system. Bradykinin-induced vasodilatation is age-dependent; this is believed to be associated with the level of expression of the two bradykinin receptors (BR1 and BR2) in the vasculature. The aim of this study was to clarify bradykinin-induced vascular reactivity of spontaneously hypertensive rats (SHR) and age-matched Wistar-Kyoto rats (WKY) after 6 weeks' consumption of a drink containing bioactive tripeptides (Ile-Pro-Pro, Val-Pro-Pro and Leu-Pro-Pro)...
June 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28819685/cardiomyocyte-dimethylarginine-dimethylaminohydrolase-1-ddah1-plays-an-important-role-in-attenuating-ventricular-hypertrophy-and-dysfunction
#8
Xin Xu, Ping Zhang, Dongmin Kwak, John Fassett, Wenhui Yue, Dorothee Atzler, Xinli Hu, Xiaohong Liu, Huan Wang, Zhongbing Lu, Haipeng Guo, Edzard Schwedhelm, Rainer H Böger, Peijie Chen, Yingjie Chen
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases that limits nitric oxide bioavailability. Dimethylarginine dimethylaminohydrolase-1 (DDAH1) exerts a critical role for ADMA degradation and plays an important role in NO signaling. In the heart, DDAH1 is observed in endothelial cells and in the sarcolemma of cardiomyocytes. While NO signaling is important for cardiac adaptation to stress, DDAH1 impact on cardiomyocyte homeostasis is not clear. Here we used the MerCreMer-LoxP model to specifically disrupt cardiomyocyte DDAH1 expression in adult mice to determine the physiological impact of cardiomyocyte DDAH1 under basal conditions and during hypertrophic stress imposed by transverse aortic constriction (TAC)...
August 17, 2017: Basic Research in Cardiology
https://www.readbyqxmd.com/read/28819363/combined-analysis-of-endothelial-hematopoietic-and-mesenchymal-stem-cell-compartments-shows-simultaneous-but-independent-effects-of-age-and-heart-disease
#9
Carine Ghem, Lucinara Dadda Dias, Roberto Tofani Sant'Anna, Renato A K Kalil, Melissa Markoski, Nance Beyer Nardi
Clinical trials using stem cell therapy for heart diseases have not reproduced the initial positive results obtained with animal models. This might be explained by a decreased regenerative capacity of stem cells collected from the patients. This work aimed at the simultaneous investigation of endothelial stem/progenitor cells (EPCs), mesenchymal stem/progenitor cells (MSCs), and hematopoietic stem/progenitor cells (HSCs) in sternal bone marrow samples of patients with ischemic or valvular heart disease, using flow cytometry and colony assays...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28819082/dysregulation-of-calpain-proteolytic-systems-underlies-degenerative-vascular-disorders
#10
Takuro Miyazaki, Akira Miyazaki
Chronic vascular diseases such as atherosclerosis, aneurysms, diabetic angiopathy/retinopathy as well as fibrotic and proliferative vascular diseases are generally complicated by the progression of degenerative insults, which are characterized by endothelial dysfunction, apoptotic/necrotic cell death in vascular/immune cells, remodeling of extracellular matrix or breakdown of elastic lamella. Increasing evidence suggests that dysfunctional calpain proteolytic systems and defective calpain protein metabolism in blood vessels contribute to degenerative disorders...
August 17, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28818791/low-density-lipoprotein-modified-by-myeloperoxidase-oxidants-induces-endothelial-dysfunction
#11
Adrian I Abdo, Benjamin S Rayner, David M van Reyk, Clare L Hawkins
Low-density lipoprotein (LDL) modified by hypochlorous acid (HOCl) produced by myeloperoxidase (MPO) is present in atherosclerotic lesions, where it is implicated in the propagation of inflammation and acceleration of lesion development by multiple pathways, including the induction of endothelial dysfunction. Thiocyanate (SCN(-)) ions are utilised by MPO to produce the oxidant hypothiocyanous acid (HOSCN), which reacts with LDL in a different manner to HOCl. Whilst the reactivity of HOCl-modified LDL has been previously studied, the role of HOSCN in the modification of LDL in vivo is poorly defined, although emerging evidence suggests that these particles have distinct biological properties...
August 5, 2017: Redox Biology
https://www.readbyqxmd.com/read/28817980/pathways-to-pulmonary-hypertension-in-sickle-cell-disease-the-search-for-prevention-and-early-intervention
#12
Natalie R Shilo, Claudia R Morris
Pulmonary hypertension (PH) develops in a significant number of patients with sickle cell disease (SCD), resulting in increased morbidity and mortality. This review focuses on PH pathophysiology, risk stratification, and new recommendations for screening and treatment for patients with SCD. Areas covered: An extensive PubMed literature search was performed. While the pathophysiology of PH in SCD is yet to be fully deciphered, it is known that the etiology is multifactorial; hemolysis, hypercoagulability, hypoxemia, ischemic-reperfusion injury, oxidative stress, and genetic susceptibility all contribute in varying degrees to endothelial dysfunction...
August 18, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28817808/ppar%C3%AE-agonist-stimulated-angiogenesis-by-improving-endothelial-precursor-cell-function-via-a-nlrp3-inflammasome-pathway
#13
Yaping Deng, Xue Han, Zheng Yao, Yuannan Sun, Jiawen Yu, Jian Cai, Guofei Ren, Guojun Jiang, Feng Han
BACKGROUND: Impaired wound healing is a common complication of diabetes and is the leading cause of lower extremity amputation. Treatment with fenofibrate, a peroxisome proliferators-activated receptor α (PPARα) agonist, was associated with a lower risk of amputations, particularly minor amputations without known large-vessel diseases, probably through non-lipid mechanisms. The current study aimed to test our hypothesis that fenofibrate stimulates angiogenesis and restores endothelial precursor cell (EPC) function via inhibiting Nod-like receptor protein 3 (NLRP3) inflammasome in streptozotocin (STZ)-induced diabetic mice...
August 16, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28817716/endothelial-dysfunction-in-renal-arcuate-arteries-of-obese-zucker-rats-the-roles-of-nitric-oxide-endothelium-derived-hyperpolarizing-factors-and-calcium-activated-k-channels
#14
Dandan Yin, Qianchen Wang, Xun Zhou, Ying Li
The roles of nitric oxide (NO), endothelium-derived hyperpolarizing factors (EDHF), and calcium-activated K+ (KCa) channels in diabetes-associated endothelial dysfunction of small renal arteries are not clear. The present study investigated acetylcholine (ACh)-induced vasorelaxation of renal arcuate arteries from obese Zucker (OZ) rats at different diabetes durations, and the relative contribution of NO, EDHF, and KCa channels to the endothelial dysfunction. OZ rats of 7 weeks (prediabetic stage), 12 weeks (early diabetic stage), and 20 weeks (late diabetic stage), and time-matched lean control rats, were studied...
2017: PloS One
https://www.readbyqxmd.com/read/28817487/inhibiting-protein-tyrosine-phosphatase-1b-to-improve-regenerative-functions-of-endothelial-cells
#15
Yuan Wang, Feng Yan, Wenjing Zhang, Shu Pang, Fan Jiang
Protein tyrosine phosphatase-1B (PTP1B) is an important negative regulator of insulin receptor- and vascular endothelial growth factor receptor-dependent signalings in endothelial cells. Genetic or pharmacological inhibition of PTP1B has been shown to enhance endothelial cell proliferation and migration, and increase nitric oxide production. In vivo, inhibiting PTP1B can reverse endothelial dysfunction, promote angiogenesis, and accelerate wound healing. Intense research is currently continuing in an effort to discover novel selective PTP1B inhibitors, primarily for treating insulin resistance...
August 4, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28816059/atherothrombosis-and-oxidative-stress-mechanisms-and-management-in-elderly
#16
Francesco Violi, Lorenzo Loffredo, Roberto Carnevale, Pasquale Pignatelli, Daniele Pastori
SIGNIFICANCE The incidence of cardiovascular events increases by aging, representing the main cause of death in old population. Aging is associated with over-production of reactive oxygen species (ROS), which may affect clotting and platelet activation, and impair endothelial function so predisposing elderly patients to thrombotic complications. RECENT ADVANCES There are increasing evidences to suggest that aging is associated with an imbalance between oxidative stress and antioxidant status. Thus, up-regulation of ROS-producing enzymes such as nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and myeloperoxidase, along with down-regulation of antioxidant enzymes, such as superoxide dismutase and glutathione peroxidase, occur during aging...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28815607/a-3d-tri-culture-system-reveals-that-activin-receptor-like-kinase-5-and-connective-tissue-growth-factor-drive-human-glomerulosclerosis
#17
John P Waters, Yvonne C Richards, Jeremy N Skepper, Mark Southwood, Paul D Upton, Nicholas W Morrell, Jordan S Pober, John R Bradley
Glomerular scarring, known as glomerulosclerosis, occurs in many chronic kidney diseases and involves interaction between glomerular endothelial cells (GEC), podocytes and mesangial cells (MCs), leading to signals that promote extracellular matrix deposition and endothelial cell dysfunction and loss. We describe a 3D tri-culture system to model human glomerulosclerosis. In 3D monoculture, each cell type alters its phenotype in response to TGFβ, which has been implicated as an important mediator of glomerulosclerosis...
August 16, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28814745/suppression-of-grk2-expression-reduces-endothelial-dysfunction-by-restoring-glucose-homeostasis
#18
Kumiko Taguchi, Mari Hida, Mami Hasegawa, Haruka Narimatsu, Takayuki Matsumoto, Tsuneo Kobayashi
Despite the associations between diabetic complications and vascular endothelial dysfunction, a direct therapeutic method targeting endothelial dysfunction remains poorly characterized. We have previously shown that chemical inhibition of G-protein-coupled receptor kinase 2 (GRK2) slightly enhances insulin sensitivity and reduces endothelial dysfunction in type 2 diabetic mice. In this study, we identified GRK2 as a novel therapeutic target of diabetic endothelial dysfunction and investigated the effect on diabetic endothelial dysfunction through the systemic administration of GRK2 siRNA using a hydrodynamic-based procedure, resulting in suppression of increased GRK2 protein levels in the liver...
August 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28814621/endothelial-cell-function-and-dysfunction-in-critically-ill-children
#19
REVIEW
Richard W Pierce, John S Giuliano, Jordan S Pober
Endothelial cells (ECs) line the lumen of the entire vascular system and actively regulate blood flow; maintain blood fluidity; control water, solute, and macromolecular transfer between blood and tissue; and modulate circulating immune cell recruitment and activation. These vital functions, combined with the broad anatomic distribution of ECs, implicate them in all forms of critical illness. The present article discusses how ECs adapt and break down during the course of critical illness. We first review the biology of ECs, highlighting the vascular segmental differences and their specific roles in the maintenance of homeostasis...
June 1, 2017: Pediatrics
https://www.readbyqxmd.com/read/28814331/circulating-levels-of-soluble-fas-scd95-are-associated-with-risk-for-development-of-a-nonresolving-acute-kidney-injury-subphenotype
#20
Pavan K Bhatraju, Cassianne Robinson-Cohen, Carmen Mikacenic, Susanna Harju-Baker, Victoria Dmyterko, Natalie S J Slivinski, W Conrad Liles, Jonathan Himmelfarb, Susan R Heckbert, Mark M Wurfel
BACKGROUND: Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different. METHODS: We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome...
August 17, 2017: Critical Care: the Official Journal of the Critical Care Forum
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