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https://www.readbyqxmd.com/read/28527699/at1-receptor-signaling-pathways-in-the-cardiovascular-system
#1
REVIEW
Tatsuo Kawai, Steven J Forrester, Shannon O'Brien, Ariele Baggett, Victor Rizzo, Satoru Eguchi
The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins...
May 17, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28526834/the-transcription-factor-irf6-co-represses-ppar%C3%AE-mediated-cytoprotection-in-ischemic-cerebrovascular-endothelial-cells
#2
Rongzhong Huang, Zicheng Hu, Yuxing Feng, Lehua Yu, Xingsheng Li
Activation of peroxisome proliferator-activated receptor gamma (PPARγ) in the cerebrovascular endothelium is a key suppressor of post-stroke brain damage. However, the role of PPARγ's co-regulators during cerebral ischemia remains largely unknown. Here, we show that the transcription factor IRF6 is a novel PPARγ co-regulator that directly binds to and suppresses PPARγ activity in murine cerebrovascular endothelial cells. Moreover, IRF6 was also revealed to be a transcriptional target of PPARγ suppression, with PPARγ silencing significantly promoting IRF6 expression in cerebrovascular endothelial cells...
May 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28526762/exacerbation-of-thromboinflammation-by-hyperglycemia-precipitates-cerebral-infarct-growth-and-hemorrhagic-transformation
#3
Jean-Philippe Desilles, Varouna Syvannarath, Véronique Ollivier, Clément Journé, Sandrine Delbosc, Célina Ducroux, William Boisseau, Liliane Louedec, Lucas Di Meglio, Stéphane Loyau, Martine Jandrot-Perrus, Louis Potier, Jean-Baptiste Michel, Mikael Mazighi, Benoit Ho-Tin-Noé
BACKGROUND AND PURPOSE: Admission hyperglycemia is associated with a poor outcome in acute ischemic stroke. How hyperglycemia impacts the pathophysiology of acute ischemic stroke remains largely unknown. We investigated how preexisting hyperglycemia increases ischemia/reperfusion cerebral injury. METHODS: Normoglycemic and streptozotocin-treated hyperglycemic rats were subjected to transient middle cerebral artery occlusion. Infarct growth and brain perfusion were assessed by magnetic resonance imaging...
May 19, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28526381/medium-term-effect-of-sublingual-l-glutathione-supplementation-on-flow-mediated-dilation-in-subjects-with-cardiovascular-risk-factors
#4
Jonica Campolo, Stefano Bernardi, Lorena Cozzi, Silvia Rocchiccioli, Cinzia Dellanoce, Antonella Cecchettini, Annamaria Tonini, Marina Parolini, Benedetta De Chiara, Gianpaolo Micheloni, Gualtiero Pelosi, Claudio Passino, Cristina Giannattasio, Oberdan Parodi
OBJECTIVE: Supplementation of glutathione (GSH) may be a positive strategy to improve the endogenous antioxidant defense required to counteract many acute and chronic diseases. However, the efficacy of GSH treatment seems to be closely related to type of administration, degree of absorption, and increase of its concentrations. The aim of this study was to test a new sublingual formulation of L-GSH, which enters directly the systemic circulation, to assess its efficacy on circulating biochemical markers of hepatic metabolism, lipid profile, and oxidative stress and on peripheral vascular function compared with placebo in patients with cardiovascular risk factors (CVRF)...
June 2017: Nutrition
https://www.readbyqxmd.com/read/28524859/mesenchymal-stem-cells-sense-mitochondria-released-from-damaged-cells-as-danger-signals-to-activate-their-rescue-properties
#5
Meriem Mahrouf-Yorgov, Lionel Augeul, Claire Crola Da Silva, Maud Jourdan, Muriel Rigolet, Sylvie Manin, René Ferrera, Michel Ovize, Adeline Henry, Aurélie Guguin, Jean-Paul Meningaud, Jean-Luc Dubois-Randé, Roberto Motterlini, Roberta Foresti, Anne-Marie Rodriguez
Mesenchymal stem cells (MSCs) protect tissues against cell death induced by ischemia/reperfusion insults. This therapeutic effect seems to be controlled by physiological cues released by the local microenvironment following injury. Recent lines of evidence indicate that MSC can communicate with their microenvironment through bidirectional exchanges of mitochondria. In particular, in vitro and in vivo studies report that MSCs rescue injured cells through delivery of their own mitochondria. However, the role of mitochondria conveyed from somatic cells to MSC remains unknown...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28523446/in-vitro-quantification-of-luminal-denudation-after-crimping-and-balloon-dilatation-of-endothelialized-covered-stents
#6
Shigeo Ichihashi, Frederic Wolf, Thomas Schmitz-Rode, Kimihiko Kichikawa, Stefan Jockenhoevel, Petra Mela
PURPOSE: Covered stents have been demonstrated to reduce restenosis; however, the membrane's limited biocompatibility can still lead to thrombus formation. To obtain optimal surface hemocompatibility, endothelialization of the luminal surface has been proposed. However, the effect of delivery procedures, such as crimping and balloon dilatation, on the endothelial layer has not been quantified. This study investigated the impact of such procedures on endothelialized covered stents in vitro...
May 18, 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/28523173/thrombotic-responses-to-coronary-stents-bioresorbable-scaffolds-and-the-kounis-hypersensitivity-associated-acute-thrombotic-syndrome
#7
REVIEW
Nicholas G Kounis, Ioanna Koniari, Anastasios Roumeliotis, Grigorios Tsigas, George Soufras, Nicholas Grapsas, Periklis Davlouros, George Hahalis
Percutaneous transluminal coronary angioplasty with coronary stent implantation is a life-saving medical procedure that has become, nowadays, the most frequent performed therapeutic procedure in medicine. Plain balloon angioplasty, bare metal stents, first and second generation drug-eluting stents, bioresorbable and bioabsorbable scaffolds have offered diachronically a great advance against coronary artery disease and have enriched our medical armamentarium. Stented areas constitute vulnerable sites for endothelial damage, endothelial dysfunction, flow turbulence, hemorheologic changes, platelet dysfunction, coagulation changes and fibrinolytic disturbances...
April 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28522908/detection-and-characterization-of-murine-colitis-and-carcinogenesis-by-molecularly-targeted-contrast-enhanced-ultrasound
#8
Markus Brückner, Jan Heidemann, Tobias M Nowacki, Friederike Cordes, Jörg Stypmann, Philipp Lenz, Faekah Gohar, Andreas Lügering, Dominik Bettenworth
AIM: To study mucosal addressin cellular adhesion molecule-1 (MAdCAM-1) and vascular endothelial growth factor (VEGF)-targeted contrast enhanced ultrasound (CEUS) for the assessment of murine colitis and carcinogenesis. METHODS: C57BL/6 mice were challenged with 3% dextran sodium-sulfate (DSS) for three, six or nine days to study the development of acute colitis. Ultrasound was performed with and without the addition of unspecific contrast agents. MAdCAM-1-targeted contrast agent was used to detect and quantify MAdCAM-1 expression...
April 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28522850/pseudomonas-aeruginosa-exolysin-promotes-bacterial-growth-in-lungs-alveolar-damage-and-bacterial-dissemination
#9
Stéphanie Bouillot, Patrick Munro, Benoit Gallet, Emeline Reboud, François Cretin, Guillaume Golovkine, Guy Schoehn, Ina Attrée, Emmanuel Lemichez, Philippe Huber
Exolysin (ExlA) is a recently-identified pore-forming toxin secreted by a subset of Pseudomonas aeruginosa strains identified worldwide and devoid of Type III secretion system (T3SS), a major virulence factor. Here, we characterized at the ultrastructural level the lesions caused by an ExlA-secreting strain, CLJ1, in mouse infected lungs. CLJ1 induced necrotic lesions in pneumocytes and endothelial cells, resulting in alveolo-vascular barrier breakdown. Ectopic expression of ExlA in an exlA-negative strain induced similar tissue injuries...
May 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28520220/endothelial-damage-effects-of-circulating-microparticles-from-patients-with-stable-angina-is-reduced-by-aspirin-though-erk-p38-mapks-pathways
#10
Cheng Gong, Xue-Feng Shan, Xu-Lang Wang, Wei-Wei Dong, Zhe Li, D Xin-Hong Liu, Wei Zhang, Kun Xing, Feng-Jun Chang
INTRODUCTION: Platelet activation participate in the development of both coronary artery disease (CAD) and circulating microparticles (MPs). As a commonly used medicine for coronary heart disease, whether aspirin affects the function of MPs remains unclear. AIMS: This study was designed to test MPs from healthy subjects, stable angina (SA) patients before and after aspirin administration were obtained. MPs origins were tested by flow cytometry. Rat thoracic aortas were incubated with MPs (with or without aspirin) to determine the effects of MPs on expression of ERK1/2, JNKs and p38 MAPK...
May 18, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28517962/inhibition-of-the-continuum-of-radiation-induced-normal-tissue-injury-by-a-redox-active-mn-porphyrin
#11
Samuel R Birer, Chen-Ting Lee, Kingshuk Roy Choudhury, Kenneth H Young, Ivan Spasojevic, Ines Batinic-Haberle, James D Crapo, Mark W Dewhirst, Kathleen A Ashcraft
Normal tissue damage after head and neck radiotherapy involves a continuum of pathologic events to the mucosa, tongue and salivary glands. We examined the radioprotective effects of MnBuOE, a redox-active manganese porphyrin, at three stages of normal tissue damage: immediate (leukocyte endothelial cell [L/E] interactions), early (mucositis) and late (xerostomia and fibrosis) after treatment. In this study, mice received 0 or 9 Gy irradiation to the oral cavity and salivary glands ± MnBuOE treatment. Changes in leukocyte-endothelial cell interactions were measured 24 h postirradiation...
May 18, 2017: Radiation Research
https://www.readbyqxmd.com/read/28512147/nrf2-inactivation-enhances-placental-angiogenesis-in-a-preeclampsia-mouse-model-and-improves-maternal-and-fetal-outcomes
#12
Masahiro Nezu, Tomokazu Souma, Lei Yu, Hiroki Sekine, Nobuyuki Takahashi, Andrew Zu-Sern Wei, Sadayoshi Ito, Akiyoshi Fukamizu, Zsuzsanna K Zsengeller, Tomohiro Nakamura, Atsushi Hozawa, S Ananth Karumanchi, Norio Suzuki, Masayuki Yamamoto
Placental activation of the renin-angiotensin system (RAS) plays a key role in the pathogenesis of preeclampsia. Reactive oxygen species (ROS) are thought to affect placental angiogenesis, which is critical for preventing preeclampsia pathology. We examined the role of ROS in preeclampsia by genetically modifying the Keap1-Nrf2 pathway, a cellular antioxidant defense system, in a mouse model of RAS-induced preeclampsia. Nrf2 deficiency would be expected to impair cellular antioxidant responses; however, Nrf2 deficiency in preeclamptic mice improved maternal and fetal survival, ameliorated intra-uterine growth retardation, and augmented oxidative DNA damage...
May 16, 2017: Science Signaling
https://www.readbyqxmd.com/read/28510599/selective-inhibition-of-brain-endothelial-rho-kinase-2-provides-optimal-protection-of-an-in-vitro-blood-brain-barrier-from-tissue-type-plasminogen-activator-and-plasmin
#13
Be'eri Niego, Natasha Lee, Pia Larsson, T Michael De Silva, Amanda E-Ling Au, Fiona McCutcheon, Robert L Medcalf
Rho-kinase (ROCK) inhibition, broadly utilised in cardiovascular disease, may protect the blood-brain barrier (BBB) during thrombolysis from rt-PA-induced damage. While the use of nonselective ROCK inhibitors like fasudil together with rt-PA may be hindered by possible hypotensive side-effects and inadequate capacity to block detrimental rt-PA activity in brain endothelial cells (BECs), selective ROCK-2 inhibition may overcome these limitations. Here, we examined ROCK-2 expression in major brain cells and compared the ability of fasudil and KD025, a selective ROCK-2 inhibitor, to attenuate rt-PA-induced BBB impairment in an in vitro human model...
2017: PloS One
https://www.readbyqxmd.com/read/28509684/histone-complexed-dna-fragments-levels-are-associated-with-coagulopathy-endothelial-cell-damage-and-increased-mortality-after-severe-pediatric-trauma
#14
Robert T Russell, Sarah C Christiaans, Tate Nice, Morgan Banks, Vincent Mortellaro, Charity Morgan, Amy Duhachek-Stapelman, Steven J Lisco, Jeffrey D Kerby, Brant M Wagener, Mike K Chen, Jean-François Pittet
BACKGROUND: The release of damage-associated molecular pattern molecules (DAMPs) in the extracellular space secondary to injury has been shown to cause systemic activation of the coagulation system and endothelial cell damage. We hypothesized that pediatric trauma patients with increased levels of histone-complexed DNA fragments (hcDNA) would have evidence of coagulopathy and endothelial damage that would be associated with poor outcomes. METHODS: We conducted a prospective observational study of 149 pediatric trauma patients and 62 control patients at two level 1 pediatric trauma centers from 2013-2016...
May 15, 2017: Shock
https://www.readbyqxmd.com/read/28509120/complex-glomerular-pathology-of-thrombotic-microangiopathy-and-focal-segmental-glomerulosclerosis-forms-tumor-like-mass-in-a-renal-transplant-donor-with-severe-renovascular-hypertension
#15
Michio Nagata, Yutaka Yamaguchi, Daisuke Toki, Izumi Yamamoto, Hiroaki Shinmura, Hiroshi Kawaguchi
The pathogenesis of glomerular hypertension-mediated FSGS and its histological variations in humans remains unknown. A 47-year-old man developed nephrotic syndrome, renal dysfunction, and malignant hypertension 2 years after donating a kidney to his son. The donor's remnant kidney developed renal mass at an upper pole which was fed by an aberrant artery that branched from the root of the renal artery. Furthermore, the main non-aberrant renal artery demonstrated severe stenosis that caused renovascular hypertension, resulting in malignant hypertension...
May 2017: CEN Case Reports
https://www.readbyqxmd.com/read/28508859/plastic-roles-of-pericytes-in-the-blood-retinal-barrier
#16
Do Young Park, Junyeop Lee, Jaeryung Kim, Kangsan Kim, Seonpyo Hong, Sangyeul Han, Yoshiaki Kubota, Hellmut G Augustin, Lei Ding, Jin Woo Kim, Hail Kim, Yulong He, Ralf H Adams, Gou Young Koh
The blood-retinal barrier (BRB) consists of tightly interconnected capillary endothelial cells covered with pericytes and glia, but the role of the pericytes in BRB regulation is not fully understood. Here, we show that platelet-derived growth factor (PDGF)-B/PDGF receptor beta (PDGFRβ) signalling is critical in formation and maturation of BRB through active recruitment of pericytes onto growing retinal vessels. Impaired pericyte recruitment to the vessels shows multiple vascular hallmarks of diabetic retinopathy (DR) due to BRB disruption...
May 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28507986/more-than-just-a-simple-cardiac-envelope-cellular-contributions-of-the-epicardium
#17
REVIEW
Angel Dueñas, Amelia E Aranega, Diego Franco
The adult pumping heart is formed by distinct tissue layers. From inside to outside, the heart is composed by an internal endothelial layer, dubbed the endocardium, a thick myocardial component which supports the pumping capacity of the heart and exteriorly covered by a thin mesothelial layer named the epicardium. Cardiac insults such as coronary artery obstruction lead to ischemia and thus to an irreversible damage of the myocardial layer, provoking in many cases heart failure and death. Thus, searching for new pathways to regenerate the myocardium is an urgent biomedical need...
2017: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/28505627/endothelial-damage-signals-refractory-acute-kidney-injury-in-critically-ill-patients
#18
Theis S Itenov, Jens-Ulrik Jensen, Sisse R Ostrowski, Pär I Johansson, Katrin M Thormar, Jens D Lundgren, Morten H Bestle
Critically ill patients with acute kidney injury (AKI) are heterogeneous on pathophysiology and prognosis. The role of endothelial damage in the pathogenesis of refractory AKI has not been clarified. The aim was to determine if biomarkers of endothelial damage, independently of the inflammatory insult on the kidney, can predict recovery of acute kidney injury. METHODS: From the "Procalcitonin And Survival Study" multicenter intensive care unit cohort, followed for 28 days after admission, we included patients without chronic kidney disease, who survived >24 h after admission and with plasma samples at admission available for biomarker analysis...
June 2017: Shock
https://www.readbyqxmd.com/read/28503423/microrna-126-a-promising-novel-biomarker-in-peripheral-blood-for-diabetic-retinopathy
#19
Li-Li Qin, Mei-Xia An, Yan-Li Liu, Han-Chun Xu, Zhi-Qing Lu
AIM: To investigate the content of serum microRNA-126 (miR-126) and its role in screening retinal endothelial injury and early diagnosis of proliferative diabetic retinopathy. METHODS: The study included 184 serum samples, 59 samples from healthy individuals, 44 samples from diabetes mellitus (DM) patients without diabetic retinopathy (NDR), 42 from non-proliferative diabetic retinopathy (NPDR) patients and 39 samples from proliferative diabetic retinopathy (PDR) patients...
2017: International Journal of Ophthalmology
https://www.readbyqxmd.com/read/28502961/haptoglobin-reduces-inflammatory-cytokine-inf-%C3%AE-and-facilitates-clot-formation-in-acute-severe-burn-rat-model
#20
Hiroyuki Koami, Yuichiro Sakamoto, Taku Miyasho, Ryo Noguchi, Norio Sato, Keita Kai, Kosuke Chris Yamada, Satoshi Inoue
Haptoglobin exerts renal protective function by scavenging free hemoglobin from the urine and blood stream in patients with hemolytic disorders. Recent studies elucidate the relationships between haptoglobin and inflammation. In addition, coagulopathy is often induced by systemic inflammation characterized by the presence of vascular endothelial damage. We hypothesize that haptoglobin might have an anti-inflammatory effect and affect hypercoagulability using rat burn model. Thirty anesthetized rats of six-weeks of age received over 30% full-thickness scald burn on the dorsal skin surface...
2017: Journal of Nippon Medical School, Nippon Ika Daigaku Zasshi
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