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https://www.readbyqxmd.com/read/27903536/persistent-microvascular-obstruction-after-myocardial-infarction-culminates-in-the-confluence-of-ferric-iron-oxide-crystals-proinflammatory-burden-and-adverse-remodeling
#1
Avinash Kali, Ivan Cokic, Richard Tang, Alice Dohnalkova, Libor Kovarik, Hsin-Jung Yang, Andreas Kumar, Frank S Prato, John C Wood, David Underhill, Eduardo Marbán, Rohan Dharmakumar
BACKGROUND: Emerging evidence indicates that persistent microvascular obstruction (PMO) is more predictive of major adverse cardiovascular events than myocardial infarct (MI) size. But it remains unclear how PMO, a phenomenon limited to the acute/subacute period of MI, drives adverse remodeling in chronic MI setting. We hypothesized that PMO resolves into chronic iron crystals within MI territories, which in turn are proinflammatory and favor adverse remodeling post-MI. METHODS AND RESULTS: Canines (n=40) were studied with cardiac magnetic resonance imaging to characterize the spatiotemporal relationships among PMO, iron deposition, infarct resorption, and left ventricular remodeling between day 7 (acute) and week 8 (chronic) post-MI...
November 2016: Circulation. Cardiovascular Imaging
https://www.readbyqxmd.com/read/27886550/v%C3%AE-1-%C3%AE-%C3%AE-t-early-cardiac-infiltrated-innate-population-dominantly-producing-il-4-protect-mice-against-cvb3-myocarditis-by-modulating-ifn%C3%AE-t-response
#2
Fangfang Wan, Kepeng Yan, Dan Xu, Qian Qian, Hui Liu, Min Li, Wei Xu
Viral myocarditis (VMC) is an inflammation of the myocardium closely associated with Coxsackievirus B3 (CVB3) infection. Vγ1(+)γδT cells, one of early cardiac infiltrated innate population, were reported to protect CVB3 myocarditis while the precise mechanism not fully addressed. To explore cytokine profiles and kinetics of Vγ1(+)γδT and mechanism of protection against VMC, flow cytometry was conducted on cardiac Vγ1 cells in C57BL/6 mice following CVB3 infection. The level of cardiac inflammation, transthoracic echocardiography and viral replication were evaluated after monoclonal antibody depletion of Vγ1γδT...
November 22, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27884253/the-quest-for-new-approaches-in%C3%A2-myocarditis-and-inflammatory%C3%A2-cardiomyopathy
#3
REVIEW
Stephane Heymans, Urs Eriksson, Jukka Lehtonen, Leslie T Cooper
Myocarditis is a diverse group of heart-specific immune processes classified by clinical and histopathological manifestations. Up to 40% of dilated cardiomyopathy is associated with inflammation or viral infection. Recent experimental studies revealed complex regulatory roles for several microribonucleic acids and T-cell and macrophage subtypes. Although the prevalence of myocarditis remained stable between 1990 and 2013 at about 22 per 100,000 people, overall mortality from cardiomyopathy and myocarditis has decreased since 2005...
November 29, 2016: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/27882934/macrophage-dependent-il-1%C3%AE-production-induces-cardiac-arrhythmias-in-diabetic-mice
#4
Gustavo Monnerat, Micaela L Alarcón, Luiz R Vasconcellos, Camila Hochman-Mendez, Guilherme Brasil, Rosana A Bassani, Oscar Casis, Daniela Malan, Leonardo H Travassos, Marisa Sepúlveda, Juan Ignacio Burgos, Martin Vila-Petroff, Fabiano F Dutra, Marcelo T Bozza, Claudia N Paiva, Adriana Bastos Carvalho, Adriana Bonomo, Bernd K Fleischmann, Antonio Carlos Campos de Carvalho, Emiliano Medei
Diabetes mellitus (DM) encompasses a multitude of secondary disorders, including heart disease. One of the most frequent and potentially life threatening disorders of DM-induced heart disease is ventricular tachycardia (VT). Here we show that toll-like receptor 2 (TLR2) and NLRP3 inflammasome activation in cardiac macrophages mediate the production of IL-1β in DM mice. IL-1β causes prolongation of the action potential duration, induces a decrease in potassium current and an increase in calcium sparks in cardiomyocytes, which are changes that underlie arrhythmia propensity...
November 24, 2016: Nature Communications
https://www.readbyqxmd.com/read/27878326/a-novel-72-kda-leukocyte-derived-osteoglycin-enhances-the-activation-of-toll-like-receptor-4-and-exacerbates-cardiac-inflammation-during-viral-myocarditis
#5
Marieke Rienks, Anna Papageorgiou, Kristiaan Wouters, Wouter Verhesen, Rick van Leeuwen, Paolo Carai, Georg Summer, Dirk Westermann, Stephane Heymans
BACKGROUND: Viral myocarditis can severely damage the myocardium through excessive infiltration of immune cells. Osteoglycin (OGN) is part of the small leucine-rich repeat proteoglycan (SLRP) family. SLRP's may affect inflammatory and fibrotic processes, but the implication of OGN in cardiac inflammation and the resulting injury upon viral myocarditis is unknown. METHODS AND RESULTS: This study uncovered a previously unidentified 72-kDa variant of OGN that is predominant in cardiac human and mouse samples of viral myocarditis...
November 23, 2016: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/27870968/the-cardiac-maladaptive-atf3-dependent-cross-talk-between-cardiomyocytes-and-macrophages-is-mediated-by-the-ifn%C3%AE-cxcl10-cxcr3-axis
#6
L Koren, U Barash, Y Zohar, N Karin, A Aronheim
RATIONAL: Pressure overload induces adaptive and maladaptive cardiac remodeling processes in the heart. Part of the maladaptive process is the cross-talk between cardiomyocytes and macrophages which is dependent on the function of the Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in cardiomyocytes-macrophages communication leading to macrophages recruitment to the heart and cardiac maladaptive remodeling is currently unknown. METHODS AND RESULTS: Isolated peritoneal macrophages from either wild type or ATF3-KO mice were cultured in serum free medium to collect conditioned medium (CM)...
November 10, 2016: International Journal of Cardiology
https://www.readbyqxmd.com/read/27856486/myocardial-immunocompetent-cells-and-macrophage-phenotypes-as%C3%A2-histopathological-surrogates-for-diagnosis-of-cardiac-sarcoidosis-in-japanese
#7
Yasuyuki Honda, Toshiyuki Nagai, Yoshihiko Ikeda, Mamoru Sakakibara, Naoya Asakawa, Nobutaka Nagano, Michikazu Nakai, Kunihiro Nishimura, Yasuo Sugano, Keiko Ohta-Ogo, Yasuhide Asaumi, Takeshi Aiba, Hideaki Kanzaki, Kengo Kusano, Teruo Noguchi, Satoshi Yasuda, Hiroyuki Tsutsui, Hatsue Ishibashi-Ueda, Toshihisa Anzai
BACKGROUND: The histological diagnosis of cardiac sarcoidosis (CS) is based on the presence of myocardial granulomas; however, the sensitivity of endomyocardial biopsy is relatively low. We investigated whether immunocompetent cells including dendritic cells (DC) and macrophages in nongranuloma sections of endomyocardial biopsy samples could be histopathological surrogates for CS diagnosis. METHODS AND RESULTS: The numbers of DC and macrophages were investigated in 95 consecutive CS patients and 50 patients with nonischemic cardiomyopathy as controls...
November 17, 2016: Journal of the American Heart Association
https://www.readbyqxmd.com/read/27856230/a-comparison-in-therapeutic-efficacy-of-several-time-points-of-intravenous-stembell-administration-in-a-rat-model-of-acute-myocardial-infarction
#8
Reindert W Emmens, Maikel Oedayrajsingh-Varma, Linde Woudstra, Otto Kamp, Elisa Meinster, Annemieke van Dijk, Marco N Helder, Diana Wouters, Sacha Zeerleder, S Marieke van Ham, Nico de Jong, Hans W M Niessen, Lynda J M Juffermans, Paul A J Krijnen
BACKGROUND: Adipose-derived stromal cells (ASCs) are a promising new therapeutic option for patients with acute myocardial infarction (AMI). Previously, we found that ASCs coupled to antibody-targeted microbubbles (StemBells [StBs]) improved cardiac function when administered intravenously 7 days post-AMI in rats. In this study, we compared the efficacy of intravenous StB administration at different administration time points following AMI in rats. METHODS: AMI, followed by reperfusion, was induced in four groups of male Wistar rats, which subsequently received an intravenous 1 × 10(6) StB bolus 1 day post-AMI (StB1; n = 8), 7 days post-AMI (StB7; n = 9), at both time points (StB1+7; n = 7) or neither (Control; n = 7)...
November 14, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27854328/parenchymal-and-stromal-cells-contribute-to-pro-inflammatory-myocardial-environment-at-early-stages-of-diabetes-protective-role-of-resveratrol
#9
Monia Savi, Leonardo Bocchi, Roberto Sala, Caterina Frati, Costanza Lagrasta, Denise Madeddu, Angela Falco, Serena Pollino, Letizia Bresciani, Michele Miragoli, Massimiliano Zaniboni, Federico Quaini, Daniele Del Rio, Donatella Stilli
Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues...
November 16, 2016: Nutrients
https://www.readbyqxmd.com/read/27833128/qishen-granules-inhibit-myocardial-inflammation-injury-through-regulating-arachidonic-acid-metabolism
#10
Chun Li, Jing Wang, Qiyan Wang, Yi Zhang, Na Zhang, Linghui Lu, Yan Wu, Qian Zhang, Wei Wang, Yong Wang, Pengfei Tu
Qishen granules (QSG), a traditional Chinese medicine, have been prescribed widely in the treatment of coronary heart diseases. Previous studies demonstrated that QSG had anti-inflammatory and cardio-protective effects in mice with acute myocardial infarction (AMI). However, the mechanisms by which QSG attenuate inflammation and prevent post-AMI heart failure (HF) are still unclear. In this study, we explored the anti-inflammatory mechanisms of QSG by in vitro and in vivo experiments. A novel inflammatory injury model of H9C2 cells was induced by lipopolysaccharide (LPS)-stimulated macrophage-conditioned media (CM)...
November 11, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27830572/inflammation-associated-co-morbidity-between-depression-and-cardiovascular-disease
#11
Angelos Halaris
Morbidity and mortality of cardiovascular disease (CVD) is exceedingly high worldwide. Depressive illness is a serious psychiatric illness that afflicts a significant portion of the world population. Epidemiological studies have confirmed the high co-morbidity between these two disease entities. The co-morbidity is bidirectional and the mechanisms responsible for it are complex and multifaceted. In addition to genetic, biological systems, psychosocial, and behavioral factors that are involved include the central and autonomic nervous systems, the neuroendocrine, immune, and the vascular and hematologic systems...
November 10, 2016: Current Topics in Behavioral Neurosciences
https://www.readbyqxmd.com/read/27830026/puerarin-inhibits-cardiac-fibrosis-via-monocyte-chemoattractant-protein-mcp-1-and-the-transforming-growth-factor-%C3%AE-1-tgf-%C3%AE-1-pathway-in-myocardial-infarction-mice
#12
Zhiwen Tao, Yingbin Ge, Ningtian Zhou, Yunle Wang, Weili Cheng, Zhijian Yang
Transforming growth factor-β1 (TGF-β1) and inflammation play important roles in the cardiac fibrosis development associated with myocardial infarction (MI). Puerarin is wildly used for treatment of diabetes, cardiovascular disease and cerebrovascular disease in China, and recently some studies have shown its anti-cardiac fibrotic effect on myocardial hypertrophy. The purpose of our study was to determine whether puerarin has an anti-cardiac fibrotic effect after MI and find the potential mechanism. A mouse model of MI was established by standard LAD coronary artery ligation, and cardiac fibrosis was confirmed by Masson's staining and the expression of collagen I, III and α-SMA...
2016: American Journal of Translational Research
https://www.readbyqxmd.com/read/27827458/microrna-126-overexpression-rescues-diabetes-induced-impairment-in-efferocytosis-of-apoptotic-cardiomyocytes
#13
Sahana Suresh Babu, Rajarajan A Thandavarayan, Darukeshwara Joladarashi, Prince Jeyabal, Shashirekha Krishnamurthy, Arvind Bhimaraj, Keith A Youker, Prasanna Krishnamurthy
Efferocytosis, a process of clearance of apoptotic cells by phagocytes, is essential for successful resolution of inflammation and maintenance of tissue homeostasis. Diabetes compromises the function of macrophages leading to adverse inflammatory response during wound healing, myocardial injury, atherosclerosis and autoimmune disorders. However, the effect of diabetes on macrophage-mediated efferocytosis of apoptotic cardiomyocytes (ACM) and the molecular mechanisms involved are not understood so far. In the present study we found that invitro efferocytosis of ACM was impaired in macrophages from db/db (diabetic) mice...
November 9, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27820939/protease-activated-receptor-1-enhances-poly-i-c-induction-of-the-antiviral-response-in-macrophages-and-mice
#14
Silvio Antoniak, Kohei Tatsumi, Michael Bode, Swetha Vanja, Julie C Williams, Nigel Mackman
The coagulation cascade is activated during viral infections as part of the host defense system. Coagulation proteases activate cells by cleavage of protease-activated receptors (PARs). Recently, we reported that the activation of PAR-1 enhanced interferon (IFN)β and CXCL10 expression in cardiac fibroblasts and in the hearts of mice infected with Coxsackievirus B3. In this study, we used the double-stranded RNA mimetic polyinosinic:polycytidylic acid (poly I:C) to induce an antiviral response in macrophages and mice...
November 8, 2016: Journal of Innate Immunity
https://www.readbyqxmd.com/read/27806233/fulminant-myocarditis-with-combination-immune-checkpoint-blockade
#15
Douglas B Johnson, Justin M Balko, Margaret L Compton, Spyridon Chalkias, Joshua Gorham, Yaomin Xu, Mellissa Hicks, Igor Puzanov, Matthew R Alexander, Tyler L Bloomer, Jason R Becker, David A Slosky, Elizabeth J Phillips, Mark A Pilkinton, Laura Craig-Owens, Nina Kola, Gregory Plautz, Daniel S Reshef, Jonathan S Deutsch, Raquel P Deering, Benjamin A Olenchock, Andrew H Lichtman, Dan M Roden, Christine E Seidman, Igor J Koralnik, Jonathan G Seidman, Robert D Hoffman, Janis M Taube, Luis A Diaz, Robert A Anders, Jeffrey A Sosman, Javid J Moslehi
Immune checkpoint inhibitors have improved clinical outcomes associated with numerous cancers, but high-grade, immune-related adverse events can occur, particularly with combination immunotherapy. We report the cases of two patients with melanoma in whom fatal myocarditis developed after treatment with ipilimumab and nivolumab. In both patients, there was development of myositis with rhabdomyolysis, early progressive and refractory cardiac electrical instability, and myocarditis with a robust presence of T-cell and macrophage infiltrates...
November 3, 2016: New England Journal of Medicine
https://www.readbyqxmd.com/read/27790620/immune-modulation-of-cardiac-repair-and-regeneration-the-art-of-mending-broken-hearts
#16
REVIEW
Ivana Zlatanova, Cristina Pinto, Jean-Sébastien Silvestre
The accumulation of immune cells is among the earliest responses that manifest in the cardiac tissue after injury. Both innate and adaptive immunity coordinate distinct and mutually non-exclusive events governing cardiac repair, including elimination of the cellular debris, compensatory growth of the remaining cardiac tissue, activation of resident or circulating precursor cells, quantitative and qualitative modifications of the vascular network, and formation of a fibrotic scar. The present review summarizes the mounting evidence suggesting that the inflammatory response also guides the regenerative process following cardiac damage...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27785882/naoxintong-attenuates-ischaemia-reperfusion-injury-through-inhibiting-nlrp3-inflammasome-activation
#17
Yaqiong Wang, Xiaoxiang Yan, Shouling Mi, Zhang Li, Yuexiang Wang, Hong Zhu, Xiaolei Sun, Buchang Zhao, Chao Zhao, Yunzeng Zou, Kai Hu, Xiaoqiang Ding, Aijun Sun, Junbo Ge
Naoxintong (NXT) is a Chinese Materia Medica standardized product extracted from 16 various kinds of Chinese traditional herbal medicines including Salvia miltiorrhiza, Angelica sinensis, Astragali Radix. Naoxintong is clinically effective in treating ischaemia heart disease. Nucleotide-binding oligomerization domain-Like Receptor with a Pyrin domain 3 (NLRP3) inflammasome has been critically involved in myocardial ischaemia/reperfusion (I/R) injury. Here, we have been suggested that NXT might attenuate myocardial I/R injury via suppression of NLRP3 inflammasome activation...
October 26, 2016: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/27779186/pkm2-dependent-glycolysis-promotes-nlrp3-and-aim2-inflammasome-activation
#18
Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang, Lizhi Cao, Jianxin Jiang, Daolin Tang
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages...
October 25, 2016: Nature Communications
https://www.readbyqxmd.com/read/27774071/characterization-of-a-mouse-model-of-emphysema-induced-by-multiple-instillations-of-low-dose-elastase
#19
Milena V Oliveira, Soraia C Abreu, Gisele A Padilha, Nazareth N Rocha, Lígia A Maia, Christina M Takiya, Debora G Xisto, Bela Suki, Pedro L Silva, Patricia R M Rocco
Many experimental models have been proposed to study the pathophysiological features of emphysema, as well as to search for new therapeutic approaches for acute or chronically injured lung parenchyma. We aimed to characterize an emphysema model induced by multiple instillations of elastase by tracking changes in inflammation, remodeling, and cardiac function after each instillation. Forty-eight C57BL/6 mice were randomly assigned across two groups. Emphysema (ELA) animals received 1, 2, 3, or 4 intratracheal instillations of pancreatic porcine elastase (PPE, 0...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27754302/lbos-02-03-the-infiltrating-macrophage-secreted-galectin-3-plays-an-essential-role-in-cardiac-fibrosis-and-diastolic-function-in-murine-pressure-overload-model
#20
Jin-Jer Chen, Wen-Rui Hao, Kuan-Cheng Chang, Ju-Chi Liu
OBJECTIVE: Cardiac fibrosis is the major pathophysiological process, contributing to the development of diastolic heart failure. We examine the role of macrophage-derived galectin-3 (gal-3) in cardiac fibrosis and diastolic function in response to transverse aortic constriction (TAC). DESIGN AND METHOD: wild-type (WT) and gal-3 knock-out (KO) mice subjected to TAC; immunohistochemistry for myocardial macrophage infiltration,gal-3,and CTGF (connective tissue growth factor) expression; picrosirius red stain for myocardial fibrosis; FACS flow- cytometry for defining the origin of myocardial macrophages...
September 2016: Journal of Hypertension
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