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https://www.readbyqxmd.com/read/28915632/decitabine-inhibits-t-cell-proliferation-via-a-novel-tet2-dependent-mechanism-and-exerts-potent-protective-effect-in-mouse-auto-and-allo-immunity-models
#1
Xue Wang, Jun Wang, Yong Yu, Tonghui Ma, Ping Chen, Bing Zhou, Ran Tao
Multiple sclerosis (MS) is an autoimmune disease characterized by the dysregulated immune response including innate and adaptive immune responses. Increasing evidence has proven the importance of epigenetic modification in the progression of MS. Recent studies revealed that low-dose decitabine (Dec, 5-Aza-2'-deoxycytidine), which incorporates into replicating DNA and inhibits DNA methylation, could prevent experimental autoimmune encephalomyelitis (EAE) development by increasing the number of regulatory T cells (Tregs)...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28911177/deoxycorticosterone-salt-mediated-cardiac-inflammation-and-fibrosis-are-dependent-on-functional-clock-signaling-in-male-mice
#2
Elizabeth K Fletcher, James Morgan, David R Kennaway, Laura A Bienvenu, Amanda J Rickard, Lea M D Delbridge, Peter J Fuller, Colin D Clyne, Morag J Young
Activation of the mineralocorticoid receptor (MR) promotes inflammation, fibrosis, and hypertension. Clinical and experimental studies show that MR antagonists have significant therapeutic benefit for all-cause heart failure; however, blockade of renal MRs limits their widespread use. Identification of key downstream signaling mechanisms for the MR in the cardiovascular system may enable development of targeted MR antagonists with selectivity for pathological MR signaling and lower impact on physiological renal electrolyte handling...
September 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28903498/from-the-cover-lifelong-exposure-of-c57bl-6n-male-mice-to-bisphenol-a-or-bisphenol-s-reduces-recovery-from-a-myocardial-infarction
#3
Amanda Kasneci, Jun Seong Lee, Tae Jin Yun, Jijun Shang, Shaun Lampen, Tamar Gomolin, Cheolho C Cheong, Lorraine E Chalifour
Bisphenol A (BPA) leaches from plastics to contaminate foodstuffs. Analogs, such as bisphenol S (BPS), are now used increasingly in manufacturing. Greater BPA exposure has been correlated with exacerbation of cardiovascular disease, including myocardial infarction (MI). To test the hypothesis that bisphenol exposure impairs cardiac healing, we exposed C57bl/6n mice to water containing 25ng/ml BPA or BPS from conception and surgically induced an MI in adult male progeny. Increased early death and cardiac dilation, and reduced cardiac function were found post-MI in BPA- and BPS-exposed mice...
September 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28882883/cytoprotective-activated-protein-c-averts-nlrp3-inflammasome-induced-ischemia-reperfusion-injury-via-mtorc1-inhibition
#4
Sumra Nazir, Ihsan Gadi, Moh'd Mohanad Al-Dabet, Ahmed Elwakiel, Shrey Kohli, Sanchita Ghosh, Jayakumar Manoharan, Satish Ranjan, Fabian Bock, Ruediger C Braun-Dullaeus, Charles T Esmon, Tobias B Huber, Eric Camerer, Chris Dockendorff, John H Griffin, Berend Isermann, Khurrum Shahzad
Cytoprotection by activated protein C (aPC) following ischemia-reperfusion injury (IRI) is associated with apoptosis inhibition. However, IRI is hallmarked by inflammation and hence conceptually cell-death forms disjunct from immunologically silent apoptosis are more likely to be relevant. As pyroptosis, cell death resulting from inflammasome activation, is typically observed in IRI we speculated that aPC ameliorates IRI by inhibiting inflammasome activation. Here we analyzed the impact of aPC on inflammasome activity in myocardial and renal IRI...
September 7, 2017: Blood
https://www.readbyqxmd.com/read/28867129/frequency-of-cholesterol-crystals-in-culprit-coronary-artery-aspirate-during-acute-myocardial-infarction-and-their-relation-to-inflammation-and-myocardial-injury
#5
George S Abela, Jagadeesh K Kalavakunta, Abed Janoudi, Dale Leffler, Gaurav Dhar, Negar Salehi, Joel Cohn, Ibrahim Shah, Milind Karve, Veera Pavan K Kotaru, Vishal Gupta, Shukri David, Keerthy K Narisetty, Michael Rich, Abigail Vanderberg, Dorothy R Pathak, Fadi E Shamoun
Cholesterol crystals (CCs) have been associated with plaque rupture through mechanical injury and inflammation. This study evaluated the presence of CCs during acute myocardial infarction (AMI) and associated myocardial injury, inflammation, and arterial blood flow before and after percutaneous coronary intervention. Patients presenting with AMI (n = 286) had aspiration of culprit coronary artery obstruction. Aspirates were evaluated for crystal content, size, composition, and morphology by scanning electron microscopy, crystallography, and infrared spectroscopy...
August 31, 2017: American Journal of Cardiology
https://www.readbyqxmd.com/read/28864347/role-of-bag3-in-cancer-progression-a-therapeutic-opportunity
#6
REVIEW
Margot De Marco, Anna Basile, Vittoria Iorio, Michelina Festa, Antonia Falco, Bianca Ranieri, Maria Pascale, Gianluca Sala, Paolo Remondelli, Mario Capunzo, Matthew A Firpo, Raffaele Pezzilli, Liberato Marzullo, Pierpaolo Cavallo, Vincenzo De Laurenzi, Maria Caterina Turco, Alessandra Rosati
BAG3 is a multifunctional protein that can bind to heat shock proteins (Hsp) 70 through its BAG domain and to other partners through its WW domain, proline-rich (PXXP) repeat and IPV (Ile-Pro-Val) motifs. Its intracellular expression can be induced by stressful stimuli, while is constitutive in skeletal muscle, cardiac myocytes and several tumour types. BAG3 can modulate the levels, localisation or activity of its partner proteins, thereby regulating major cell pathways and functions, including apoptosis, autophagy, mechanotransduction, cytoskeleton organisation, motility...
August 29, 2017: Seminars in Cell & Developmental Biology
https://www.readbyqxmd.com/read/28862949/high-perforin-positive-cardiac-cell-infiltration-and-male-sex-predict-adverse-long-term-mortality-in-patients-with-inflammatory-cardiomyopathy
#7
Felicitas Escher, Uwe Kühl, Dirk Lassner, Andrea Stroux, Ulrich Gross, Dirk Westermann, Burkert Pieske, Wolfgang Poller, Heinz-Peter Schultheiss
BACKGROUND: The authors analyzed the effects of perforin-dependent infiltration on long-term mortality in patients with inflammatory cardiomyopathy (CMi). We previously demonstrated that left ventricular function deteriorates and progresses to substantial cardiac dysfunction in patients with perforin-positive cardiac cell infiltration. METHODS AND RESULTS: Between 2003 and 2013, 2389 consecutive patients with clinically suspected CMi who underwent endomyocardial biopsies were enrolled...
August 18, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28860151/myeloid-receptor-cd36-is-required-for-early-phagocytosis-of-myocardial-infarcts-and-induction-of-nr4a1-dependent-mechanisms-of-cardiac-repair
#8
Shirley Dehn, Edward B Thorp
Phagocytosis after myocardial infarction (MI) is a prerequisite to cardiac repair. Recruited monocytes clear necrotic cardiomyocytes and differentiate into cardiac macrophages. Some studies have linked apoptotic cell receptors on cardiac macrophages to tissue repair; however, the contribution of precursor monocyte phagocytic receptors, which are the first to interact with the cardiac parenchyma, is unclear. The scavenger receptor cluster of differentiation (CD)36 protein was detected on cardiac Ly6cHI monocytes, and bone marrow-derived Cd36 was essential for both early phagocytosis of dying cardiomyocytes and for smaller infarct sizes in female and male mice after permanent coronary ligation...
August 31, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28855433/effects-of-cardiac-rehabilitation-on-high-density-lipoprotein-mediated-cholesterol-efflux-capacity-and-paraoxonase-1-activity-in-patients-with-acute-coronary-syndrome
#9
Fumiaki Furuyama, Shinji Koba, Yuya Yokota, Fumiyoshi Tsunoda, Makoto Shoji, Youichi Kobayashi
AIMS: We evaluated whether exercised-based cardiac rehabilitation (CR) can ameliorate the HDL function, i.e., cholesterol efflux capacity (CEC) and paraoxonase-1 activity in patients with acute coronary syndrome (ACS). METHODS: This study is a retrospective analysis of stored serum from patients with ACS following successful percutaneous coronary intervention. The CEC, measured by a cell-based ex vivo assay using apolipoprotein B-depleted serum and (3)H-cholesterol labeled macrophages and arylesterase activity (AREA) at the onset or early phase of ACS, and the follow-up periods were compared between 69 patients who completed the five-month outpatient CR program (CR group) and 15 patients who did not participate and/or dropped out from CR program (non-CR group)...
August 30, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28851937/serelaxin-improves-cardiac-and-renal-function-in-doca-salt-hypertensive-rats
#10
Dong Wang, Yuhuan Luo, Komuraiah Myakala, David J Orlicky, Evgenia Dobrinskikh, Xiaoxin Wang, Moshe Levi
Serelaxin, a recombinant form of the naturally occurring peptide hormone relaxin-2, is a pleiotropic vasodilating hormone that has been studied in patients with acute heart failure. In this study, the effects of serelaxin on cardiac and renal function, fibrosis, inflammation and lipid accumulation were studied in DOCA-salt treated rats. Uninephrectomized rats were assigned to two groups: controls provided with normal drinking water and DOCA provided with DOCA pellets and sodium chloride drinking water. After 4 weeks, the DOCA-salt rats were randomly selected and implanted with osmotic minipumps delivering vehicle or serelaxin for another 4 weeks...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28851810/mertk-cleavage-on-resident-cardiac-macrophages-compromises-repair-after-myocardial-ischemia-reperfusion-injury
#11
Matthew DeBerge, Xin-Yi Yeap, Shirley Dehn, Shuang Zhang, Lubov S Grigoryeva, Sol Misener, Daniele Procissi, Xin Zhou, Daniel C Lee, William A Muller, Xunrong Luo, Carla Rothlin, Ira Tabas, Edward B Thorp
Rationale: Clinical benefits of reperfusion after myocardial infarction (MI) are offset by maladaptive innate immune cell function and therapeutic interventions are lacking. Objective: We sought to test the significance of phagocytic clearance by resident and recruited phagocytes after myocardial ischemia reperfusion (I/R). Methods and Results: In humans, we discovered that clinical reperfusion after MI led to significant elevation of the soluble form of MerTK (i.e. solMER), a critical biomarker of compromised phagocytosis by innate macrophages...
August 29, 2017: Circulation Research
https://www.readbyqxmd.com/read/28842629/bone-marrow-derived-cells-and-their-conditioned-medium-induce-microvascular-repair-in-uremic-rats-by-stimulation-of-endogenous-repair-mechanisms
#12
Lina Golle, Hans U Gerth, Katrin Beul, Barbara Heitplatz, Peter Barth, Manfred Fobker, Hermann Pavenstädt, Giovana S Di Marco, Marcus Brand
The reduced number of circulating stem/progenitor cells that is found in chronic kidney disease (CKD) patients may contribute to impaired angiogenic repair and decreased capillary density in the heart. Cell therapy with bone marrow-derived cells (BMDCs) has been shown to induce positive effects on the microvasculature and cardiac function, most likely due to secretion of growth factors and cytokines, all of which are present in the conditioned medium (CM); however, this is controversial. Here we showed that treatment with BMDC or CM restored vascular density and decreased the extent of fibrosis in a rat model of CKD, the 5/6 nephrectomy...
August 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28837618/therapeutic-benefits-of-intravenous-cardiosphere-derived-cell-therapy-in-rats-with-pulmonary-hypertension
#13
Ryan C Middleton, Mario Fournier, Xuan Xu, Eduardo Marbán, Michael I Lewis
Pulmonary arterial hypertension (PAH) is a progressive condition characterized by occlusive pulmonary arteriopathy, in which survival remains poor despite pharmacologic advances. The aim of this study was to evaluate the ability of cardiosphere-derived cells (CDCs), cardiac progenitor cells with potent anti-inflammatory and immunomodulatory properties, to attenuate hemodynamic and morphometric remodeling of the right ventricle (RV) and pulmonary arterioles in rats with established monocrotaline (MCT)-induced PAH...
2017: PloS One
https://www.readbyqxmd.com/read/28835616/leukocytic-toll-like-receptor-2-deficiency-preserves-cardiac-function-and-reduces-fibrosis-in-sustained-pressure-overload
#14
Jiong-Wei Wang, Magda S C Fontes, Xiaoyuan Wang, Suet Yen Chong, Elise L Kessler, Ya-Nan Zhang, Judith J de Haan, Fatih Arslan, Saskia C A de Jager, Leo Timmers, Toon A B van Veen, Carolyn S P Lam, Dominique P V de Kleijn
An involement of Toll-like receptor 2 (TLR2) has been established in cardiac dysfunction after acute myocardial infarction; however, its role in chronic pressure overload is unclear. We sought to evaluate the role of TLR2 in cardiac hypertrophy, fibrosis and dysfunction in sustained pressure overload. We induced pressure overload via transverse aortic constriction (TAC) in TLR2(-/-) and wild type (WT) mice, and followed temporal changes over 8 weeks. Despite similar increases in heart weight, left ventricular (LV) ejection fraction (EF) and diastolic function (mitral E/A ratio) were preserved in TLR2(-/-) mice but impaired in WT mice following TAC...
August 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28832763/methotrexate-associated-to-lipid-core-nanoparticles-improves-cardiac-allograft-vasculopathy-and-the-inflammatory-profile-in-a-rabbit-heart-graft-model
#15
A I Fiorelli, D D Lourenço-Filho, E R Tavares, P O Carvalho, A F Marques, P S Gutierrez, R C Maranhão, N A G Stolf
Coronary allograft vasculopathy is an inflammatory-proliferative process that compromises the long-term success of heart transplantation and has no effective treatment. A lipid nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and concentrates them in the heart graft. The aim of the study was to investigate the effects of methotrexate (MTX) associated to LDE. Rabbits fed a 0.5% cholesterol diet and submitted to heterotopic heart transplantation were treated with cyclosporine A (10 mg·kg-1·day-1 orally) and allocated to treatment with intravenous LDE-MTX (4 mg/kg, weekly, n=10) or with weekly intravenous saline solution (control group, n=10), beginning on the day of surgery...
August 17, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28826664/aicar-treatment-reduces-interstitial-fibrosis-in-aging-mice-suppression-of-the-inflammatory-fibroblast
#16
Katarzyna A Cieslik, JoAnn Trial, Mark L Entman
In 2030, elderly people will represent 20% of the United States population. Even now, chronic cardiac diseases, especially heart failure with preserved systolic function (HFpEF), are the most expensive DRGs for Medicare. Progressive interstitial fibrosis in the aging heart is well recognized as an important component of HFpEF. Our recent studies suggested an important pathophysiologic role for reduced TGF-β receptor 1 (TGFβR1) signaling in mesenchymal stem cells (MSCs) and their mesenchymal fibroblast progeny in the development of interstitial fibrosis...
October 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28822966/inhibitory-actions-of-the-nrg-1-erbb4-pathway-in-macrophages-during-tissue-fibrosis-in-heart-skin-and-lung
#17
Zarha Vermeulen, Anne-Sophie Hervent, Lindsey Dugaucquier, Leni Vandekerckhove, Miche Rombouts, Matthias Beyens, Dorien M Schrijvers, Guido R Y De Meyer, Stuart Maudsley, Gilles W De Keulenaer, Vincent Fm Segers
The neuregulin-1 (NRG-1)/ErbB system is an endothelium-controlled paracrine system modulating cardiac performance and adaptation. Recent studies indicate that NRG-1 has anti-fibrotic effects in the left ventricle (LV), which were explained by direct actions on cardiac fibroblasts. However, the NRG-1/ErbB system also regulates the function of macrophages. In this study, we hypothesized that the anti-fibrotic effect of NRG-1 in the heart is at least partially mediated through inhibitory effects on macrophages...
August 19, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28821329/cardiac-progenitor-cell-recruitment-drives-fetal-cardiac-regeneration-by-enhanced-angiogenesis
#18
Carlos Zgheib, Maggie M Hodges, Myron W Allukian, Junwang Xu, Kara L Spiller, Joseph H Gorman, Robert C Gorman, Kenneth W Liechty
BACKGROUND: In contrast to adults, the fetal response to myocardial infarction (MI) is regenerative, requiring the recruitment of cardiac progenitor cells to replace infarcted myocardium. Macrophage contribution to tissue repair depends on their phenotype: M1 are proinflammatory and initiate angiogenesis; M2a are profibrotic and contribute to blood vessels maturation; and M2c are proremodeling and proangiogenesis. The goal of the present study was to expand on this work by examining cardiac progenitor cells recruitment, and the role of macrophages in promoting angiogenesis and cardiac regeneration in the fetal heart after MI...
August 16, 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28818266/microrna-93-elevation-after-myocardial-infarction-is-cardiac-protective
#19
Kai Li, Tao Lin, Lingdan Chen, Neng Wang
Coronary Artery Disease (CAD) is one of the most serious diseases that endangers human health worldwide, myocardial infarction (MI) is an acute form of CAD. Recent developments in MI therapies have resulted in significant reductions in mortality. However, subsequent chronic congestive heart failure and ventricle remodeling plagues an increasing number of MI patients. MicroRNAs (miR) have been reported to be involved in the process of cardiac remodeling, a recent study shows that miR-93 is elevated in the blood of CAD patients...
September 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/28815768/micro-vesicles-derived-from-human-wharton-s-jelly-mesenchymal-stromal-cells-mitigate-renal-ischemia-reperfusion-injury-in-rats-after-cardiac-death-renal-transplantation
#20
Xiaoqiang Wu, Tianzhong Yan, Zhiwei Wang, Xuan Wu, Guanghui Cao, Chan Zhang, Xiangyong Tian, Junpeng Wang
The purpose of the present study was to investigate the possible therapeutic effects of the human Wharton-Jelly mesenchymal stromal cells derived micro-vesicles (hWJMSCs-MVs) on renal ischemia-reperfusion injury (IRI) after cardiac death (CD) renal transplantation in rats. MVs were injected intravenously in rats immediately after renal transplantation. The animals were sacrificed at 24 h, 48 h, 1 and 2 weeks post-transplantation. ELISA was used to determine the von Willebrand Factor (vWF), tumor necrosis factor (TNF)-α, and interleukin (IL)-10 levels in the serum...
August 16, 2017: Journal of Cellular Biochemistry
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