Interplay Between Inflammation and Thrombosis in Cardiovascular Pathology
Total Page:16
File Type:pdf, Size:1020Kb
Load more
Recommended publications
-
Implicating Gene and Cell Networks Responsible for Differential COVID
bioRxiv preprint doi: https://doi.org/10.1101/2021.06.07.447287; this version posted June 16, 2021. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY-NC 4.0 International license. 1 Implicating Gene and Cell Networks Responsible for 2 Differential COVID-19 Host Responses via an Interactive 3 Single Cell Web Portal 4 5 Kang Jin1,2, Eric E. Bardes1, Alexis Mitelpunkt1,3,4, Jake Y. Wang1, Surbhi Bhatnagar1,5, 6 Soma Sengupta6, Daniel Pomeranz Krummel6, Marc E. Rothenberg7, Bruce J. 7 Aronow1,8,9,* 8 9 1Division oF Biomedical InFormatics, Cincinnati Children's Hospital Medical Center, 10 Cincinnati, OH, 45229, USA 11 2Department oF Biomedical InFormatics, University oF Cincinnati, Cincinnati, OH, 45229, 12 USA 13 3Pediatric Rehabilitation, Dana-Dwek Children's Hospital, Tel Aviv Medical Center, Tel 14 Aviv, 6423906, Israel 15 4Sackler Faculty oF Medicine, Tel Aviv University, Tel Aviv, 6997801, Israel 16 5Department oF Electrical Engineering and Computer Science, University oF Cincinnati, 17 Cincinnati, OH, 45221, USA 18 6Department oF Neurology and Rehabilitation Medicine, University oF Cincinnati College 19 oF Medicine, Cincinnati, OH, 45267, USA. 20 7Division oF Allergy and Immunology, Department oF Pediatrics, Cincinnati Children's 21 Hospital Medical Center, University oF Cincinnati, Cincinnati, OH, 45229, USA 22 8Department oF Pediatrics, University oF Cincinnati School oF Medicine, Cincinnati, OH, 23 45256, USA 24 9Lead contact 25 *Correspondence: [email protected] (B.A.) 26 27 28 29 30 31 1 bioRxiv preprint doi: https://doi.org/10.1101/2021.06.07.447287; this version posted June 16, 2021. -
Structural and Functional Characterization of TMEM16 Family Members
Zurich Open Repository and Archive University of Zurich Main Library Strickhofstrasse 39 CH-8057 Zurich www.zora.uzh.ch Year: 2016 Structural and functional characterization of TMEM16 family members Lim, Novandy Posted at the Zurich Open Repository and Archive, University of Zurich ZORA URL: https://doi.org/10.5167/uzh-129639 Dissertation Published Version Originally published at: Lim, Novandy. Structural and functional characterization of TMEM16 family members. 2016, University of Zurich, Faculty of Science. Structural and Functional Characterization of TMEM16 Family Members Dissertation zur Erlangung der naturwissenschaftlichen Doktorwürde (Dr. sc. nat.) vorgelegt der Mathematisch-naturwissenschaftlichen Fakultät der Universität Zürich von Novandy Karunia Lim aus Indonesien Promotionskomitee Prof. Dr. Raimund Dutzler (Vorsitz) Prof. Dr. Markus Seeger Prof. Dr. Martin Jinek Zürich, 2016 Acknowledgements I would like to take this opportunity to thank all the people who have supported and helped me throughout my stay and project in the lab. Firstly, I would like to thank Prof. Raimund Dutzler for the opportunity to work on this highly exciting project. I am sincerely grateful for his constant support and his faith in me throughout my time in his group. I would like to thank Prof. Martin Jinek and Prof. Markus Seeger for being part of my thesis committee. I would like to thank Janine Brunner and Stephan Schenck for the helpful discussion on TMEM16 project. A big thank you to Alessia Dürst too for helping us with the homologue screen during her Masters thesis. I am grateful to all the past and present members of the Dutzler for their friendship, support and scientific discussions. -
Sickle Cell Disease: a Paradigm for Venous Thrombosis Pathophysiology
International Journal of Molecular Sciences Review Sickle Cell Disease: A Paradigm for Venous Thrombosis Pathophysiology Maria A. Lizarralde-Iragorri and Arun S. Shet * Laboratory of Sickle Thrombosis and Vascular Biology, Sickle Cell Branch, National Institutes of Health, Bethesda, MD 20892, USA; [email protected] * Correspondence: [email protected] Received: 26 June 2020; Accepted: 24 July 2020; Published: 25 July 2020 Abstract: Venous thromboembolism (VTE) is an important cause of vascular morbidity and mortality. Many risk factors have been identified for venous thrombosis that lead to alterations in blood flow, activate the vascular endothelium, and increase the propensity for blood coagulation. However, the precise molecular and cellular mechanisms that cause blood clots in the venous vasculature have not been fully elucidated. Patients with sickle cell disease (SCD) demonstrate all the risk factors for venous stasis, activated endothelium, and blood hypercoagulability, making them particularly vulnerable to VTE. In this review, we will discuss how mouse models have elucidated the complex vascular pathobiology of SCD. We review the dysregulated pathways of inflammation and coagulation in SCD and how the resultant hypercoagulable state can potentiate thrombosis through down-regulation of vascular anticoagulants. Studies of VTE pathogenesis using SCD mouse models may provide insight into the intersection between the cellular and molecular processes involving inflammation and coagulation and help to identify novel mechanistic pathways. Keywords: venous thromboembolism (VTE); sickle cell disease (SCD); mice models; stasis; hypercoagulability; endothelial injury; inflammation 1. Venous Thromboembolism and Sickle Cell Disease The third most common cause of vascular death from thrombosis in the United States is venous thromboembolism (VTE), a disorder that includes both deep vein thrombosis (DVT) and pulmonary embolism (PE) [1]. -
YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6
Molecular Medicine YAP Controls Endothelial Activation and Vascular Inflammation Through TRAF6 Yang Lv, Kyungho Kim, Yue Sheng, Jaehyung Cho, Zhijian Qian, You-Yang Zhao, Gang Hu, Duojia Pan, Asrar B. Malik, Guochang Hu Rationale: Microvascular inflammation and endothelial dysfunction secondary to unchecked activation of endothelium play a critical role in the pathophysiology of sepsis and organ failure. The intrinsic signaling mechanisms responsible for dampening excessive activation of endothelial cells are not completely understood. Objective: To determine the central role of YAP (Yes-associated protein), the major transcriptional coactivator of the Hippo pathway, in modulating the strength and magnitude of endothelial activation and vascular inflammation. Methods and Results: Endothelial-specific YAP knockout mice showed increased basal expression of E-selectin and ICAM (intercellular adhesion molecule)-1 in endothelial cells, a greater number of adherent neutrophils in postcapillary venules and increased neutrophil counts in bronchoalveolar lavage fluid. Lipopolysaccharide challenge of these mice augmented NF-κB (nuclear factor-κB) activation, expression of endothelial adhesion proteins, neutrophil and monocyte adhesion to cremaster muscle venules, transendothelial neutrophil migration, and lung inflammatory injury. Deletion of YAP in endothelial cells also markedly augmented the inflammatory response and cardiovascular dysfunction in a polymicrobial sepsis model induced by cecal ligation and puncture. YAP functioned by interacting with the E3 ubiquitin-protein ligase TLR (Toll-like receptor) signaling adaptor TRAF6 (tumor necrosis factor receptor-associated factor 6) to ubiquitinate TRAF6, and thus promoted TRAF6 degradation and modification resulting in inhibition of NF-κB activation. TRAF6 depletion in endothelial cells rescued the augmented inflammatory phenotype in mice with endothelial cell–specific deletion of YAP. -
TMEM16F Activation by Ca2+ Triggers Plasma Membrane Expansion And
www.nature.com/scientificreports OPEN TMEM16F activation by Ca2+ triggers plasma membrane expansion and directs PD-1 Received: 18 September 2018 Accepted: 3 December 2018 trafcking Published: xx xx xxxx Christopher Bricogne1, Michael Fine2, Pedro M. Pereira 3, Julia Sung4, Maha Tijani4, Youxue Wang2, Ricardo Henriques 3, Mary K. Collins1,4,5 & Donald Hilgemann2 TMEM16F is a Ca2+ -gated ion channel that is required for Ca2+ -activated phosphatidylserine exposure on the surface of many eukaryotic cells. TMEM16F is widely expressed and has roles in platelet activation during blood clotting, bone formation and T cell activation. By combining microscopy and patch clamp recording we demonstrate that activation of TMEM16F by Ca2+ ionophores in Jurkat T cells triggers large-scale surface membrane expansion in parallel with phospholipid scrambling. With continued ionophore application,TMEM16F-expressing cells then undergo extensive shedding of ectosomes. The T cell co-receptor PD-1 is selectively incorporated into ectosomes. This selectivity depends on its transmembrane sequence. Surprisingly, cells lacking TMEM16F not only fail to expand surface membrane in response to elevated cytoplasmic Ca2+, but instead undergo rapid massive endocytosis with PD-1 internalisation. These results establish a new role for TMEM16F as a regulator of Ca2+ activated membrane trafcking. Eukaryotic cells retain phosphatidylserine (PS) on the cytoplasmic face of the plasma membrane1. In response to high levels of cytoplasmic Ca2+ elevation and during apoptosis, PS is exposed on the cell surface by a process known as phospholipid scrambling2. Ca2+-activated phospholipid scrambling is mediated by a transmembrane protein, TMEM16F (also known as anoctamin 6)3,4, a widely expressed member of the TMEM16 family of ion channels5. -
Supp Table 6.Pdf
Supplementary Table 6. Processes associated to the 2037 SCL candidate target genes ID Symbol Entrez Gene Name Process NM_178114 AMIGO2 adhesion molecule with Ig-like domain 2 adhesion NM_033474 ARVCF armadillo repeat gene deletes in velocardiofacial syndrome adhesion NM_027060 BTBD9 BTB (POZ) domain containing 9 adhesion NM_001039149 CD226 CD226 molecule adhesion NM_010581 CD47 CD47 molecule adhesion NM_023370 CDH23 cadherin-like 23 adhesion NM_207298 CERCAM cerebral endothelial cell adhesion molecule adhesion NM_021719 CLDN15 claudin 15 adhesion NM_009902 CLDN3 claudin 3 adhesion NM_008779 CNTN3 contactin 3 (plasmacytoma associated) adhesion NM_015734 COL5A1 collagen, type V, alpha 1 adhesion NM_007803 CTTN cortactin adhesion NM_009142 CX3CL1 chemokine (C-X3-C motif) ligand 1 adhesion NM_031174 DSCAM Down syndrome cell adhesion molecule adhesion NM_145158 EMILIN2 elastin microfibril interfacer 2 adhesion NM_001081286 FAT1 FAT tumor suppressor homolog 1 (Drosophila) adhesion NM_001080814 FAT3 FAT tumor suppressor homolog 3 (Drosophila) adhesion NM_153795 FERMT3 fermitin family homolog 3 (Drosophila) adhesion NM_010494 ICAM2 intercellular adhesion molecule 2 adhesion NM_023892 ICAM4 (includes EG:3386) intercellular adhesion molecule 4 (Landsteiner-Wiener blood group)adhesion NM_001001979 MEGF10 multiple EGF-like-domains 10 adhesion NM_172522 MEGF11 multiple EGF-like-domains 11 adhesion NM_010739 MUC13 mucin 13, cell surface associated adhesion NM_013610 NINJ1 ninjurin 1 adhesion NM_016718 NINJ2 ninjurin 2 adhesion NM_172932 NLGN3 neuroligin -
Anoctamin 1 - a Member of a Novel Family of Ion Channels with Extended Functions and Significance in Disease
UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS Anoctamin 1 - A Member of a Novel Family of Ion Channels with Extended Functions and Significance in Disease Doutoramento em Biologia Especialidade: Biologia de Sistemas Joana Ramos Rapaz Lérias Tese orientada por: Prof. Dr. Karl Kunzelmann e Prof. Dr. Margarida D. Amaral Documento especialmente elaborado para a obtenção do grau de doutor 2018 UNIVERSIDADE DE LISBOA FACULDADE DE CIÊNCIAS Anoctamin 1 - A Member of a Novel Family of Ion Channels with Extended Functions and Significance in Disease Doutoramento em Biologia Especialidade: Biologia de Sistemas Joana Ramos Rapaz Lérias Tese orientada por: Prof. Dr. Karl Kunzelmann e Prof. Dr. Margarida D. Amaral Júri: Presidente: ● Doutor Rui Manuel dos Santos Malhó, Professor Catedrático da Faculdade de Ciências da Universidade de Lisboa Vogais: ● Doutor Karl Kunzelmann, Kunzelmann, Professor, Faculty of Biology and Pre-Clinical Medicine da University of Regensburg, Alemanha (orientador); ● Doutor Ana Colette Pereira de Castro Osório Maurício, Professora Associada com Agregação, Instituto de Ciências Biomédicas Abel Salazar (ICBAS) da Universidade do Porto; ● Doutor Peter Jordan, Investigador Principal, Departamento de Genética Humana do Instituto Nacional de Saúde Doutor Ricardo Jorge; ● Doutora Maria da Graça Tavares Rebelo de Soveral Rodrigues, Professora Associada com Agregação, Faculdade de Farmácia da Universidade de Lisboa. Documento especialmente elaborado para a obtenção do grau de doutor Fundação para a Ciência e Tecnologia do Ministério da Educação e Ciência (FCT/ SFRH / BD / 52489 / 2014) 2018 De acordo com o disposto no artigo 24º do Regulamento de Estudos de Pós- Graduação da Universidade de Lisboa, Despacho nº 7024/2017, publicado no Diário da República – 2ª Série – nº 155 – 11 de Agosto de 2017, foram utilizados nesta dissertação resultados incluídos nos seguintes artigos: 1. -
Regulation and Function of TMEM16F in Renal Podocytes
International Journal of Molecular Sciences Article Regulation and Function of TMEM16F in Renal Podocytes Laura K. Schenk 1 ID , Jiraporn Ousingsawat 2, Boris V. Skryabin 3 ID , Rainer Schreiber 2,†, Hermann Pavenstädt 1,† and Karl Kunzelmann 2,*,† ID 1 Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, 48149 Muenster, Germany; [email protected] (L.K.S.); [email protected] (H.P.) 2 Institut für Physiologie, Universität Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany; [email protected] (J.O.); [email protected] (R.S.) 3 Transgenic Animal and Genetic Engineering Models (TRAM), Department of Medicine, Westfälischen, Wilhelms–Universität Münster, 48149 Münster, Germany; [email protected] * Correspondence: [email protected]; Tel.: +49-(0)941-943-4302; Fax: +49-(0)941-943-4315 † These authors contributed equally to this work. Received: 6 May 2018; Accepted: 14 June 2018; Published: 18 June 2018 Abstract: The Ca2+-activated phospholipid scramblase and ion channel TMEM16F is expressed in podocytes of renal glomeruli. Podocytes are specialized cells that form interdigitating foot processes as an essential component of the glomerular filter. These cells, which participate in generation of the primary urine, are often affected during primary glomerular diseases, such as glomerulonephritis and secondary hypertensive or diabetic nephropathy, which always leads to proteinuria. Because the function of podocytes is known to be controlled by intracellular Ca2+ signaling, it is important to know about the role of Ca2+-activated TMEM16F in these cells. To that end, we generated an inducible TMEM16F knockdown in the podocyte cell line AB8, and produced a conditional mouse model with knockout of TMEM16F in podocytes and renal epithelial cells of the nephron. -
Entrez ID Gene Name Fold Change Q-Value Description
Entrez ID gene name fold change q-value description 4283 CXCL9 -7.25 5.28E-05 chemokine (C-X-C motif) ligand 9 3627 CXCL10 -6.88 6.58E-05 chemokine (C-X-C motif) ligand 10 6373 CXCL11 -5.65 3.69E-04 chemokine (C-X-C motif) ligand 11 405753 DUOXA2 -3.97 3.05E-06 dual oxidase maturation factor 2 4843 NOS2 -3.62 5.43E-03 nitric oxide synthase 2, inducible 50506 DUOX2 -3.24 5.01E-06 dual oxidase 2 6355 CCL8 -3.07 3.67E-03 chemokine (C-C motif) ligand 8 10964 IFI44L -3.06 4.43E-04 interferon-induced protein 44-like 115362 GBP5 -2.94 6.83E-04 guanylate binding protein 5 3620 IDO1 -2.91 5.65E-06 indoleamine 2,3-dioxygenase 1 8519 IFITM1 -2.67 5.65E-06 interferon induced transmembrane protein 1 3433 IFIT2 -2.61 2.28E-03 interferon-induced protein with tetratricopeptide repeats 2 54898 ELOVL2 -2.61 4.38E-07 ELOVL fatty acid elongase 2 2892 GRIA3 -2.60 3.06E-05 glutamate receptor, ionotropic, AMPA 3 6376 CX3CL1 -2.57 4.43E-04 chemokine (C-X3-C motif) ligand 1 7098 TLR3 -2.55 5.76E-06 toll-like receptor 3 79689 STEAP4 -2.50 8.35E-05 STEAP family member 4 3434 IFIT1 -2.48 2.64E-03 interferon-induced protein with tetratricopeptide repeats 1 4321 MMP12 -2.45 2.30E-04 matrix metallopeptidase 12 (macrophage elastase) 10826 FAXDC2 -2.42 5.01E-06 fatty acid hydroxylase domain containing 2 8626 TP63 -2.41 2.02E-05 tumor protein p63 64577 ALDH8A1 -2.41 6.05E-06 aldehyde dehydrogenase 8 family, member A1 8740 TNFSF14 -2.40 6.35E-05 tumor necrosis factor (ligand) superfamily, member 14 10417 SPON2 -2.39 2.46E-06 spondin 2, extracellular matrix protein 3437 -
Omega-3 Fatty Acids Modulate Weibel-Palade Body Degranulation and Actin Cytoskeleton Rearrangement in PMA-Stimulated Human Umbilical Vein Endothelial Cells
Mar. Drugs 2013, 11, 4435-4450; doi:10.3390/md11114435 OPEN ACCESS marine drugs ISSN 1660-3397 www.mdpi.com/journal/marinedrugs Article Omega-3 Fatty Acids Modulate Weibel-Palade Body Degranulation and Actin Cytoskeleton Rearrangement in PMA-Stimulated Human Umbilical Vein Endothelial Cells Corinna S. Bürgin-Maunder, Peter R. Brooks and Fraser D. Russell * Inflammation and Healing Research Cluster, School of Health and Sport Sciences, University of the Sunshine Coast, Maroochydore, Queensland 4556, Australia; E-Mails: [email protected] (C.S.B.-M.); [email protected] (P.R.B.) * Author to whom correspondence should be addressed; E-Mail: [email protected]; Tel.: +61-7-5459-4665; Fax: +61-7-5459-4600. Received: 2 September 2013; in revised form: 15 October 2013 / Accepted: 22 October 2013 / Published: 8 November 2013 Abstract: Long chain omega-3 polyunsaturated fatty acids (LC n-3 PUFAs) produce cardiovascular benefits by improving endothelial function. Endothelial cells store von Willebrand factor (vWF) in cytoplasmic Weibel-Palade bodies (WPBs). We examined whether LC n-3 PUFAs regulate WPB degranulation using cultured human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with or without 75 or 120 µM docosahexaenoic acid or eicosapentaenoic acid for 5 days at 37 °C. WPB degranulation was stimulated using phorbol 12-myristate 13-acetate (PMA), and this was assessed by immunocytochemical staining for vWF. Actin reorganization was determined using phalloidin-TRITC staining. We found that PMA stimulated WPB degranulation, and that this was significantly reduced by prior incubation of cells with LC n-3 PUFAs. In these cells, WPBs had rounded rather than rod-shaped morphology and localized to the perinuclear region, suggesting interference with cytoskeletal remodeling that is necessary for complete WPB degranulation. -
Endothelial Cell Participation in Inflammatory Reaction
International Journal of Molecular Sciences Review Endothelial Cell Participation in Inflammatory Reaction Jean-Luc Wautier * and Marie-Paule Wautier Faculté de Médecine, Université Denis Diderot Paris, 75013 Paris, France; [email protected] * Correspondence: [email protected] Abstract: Inflammation is an old concept that has started to be considered as an important factor in infection and chronic diseases. The role of leukocytes, the plasmatic components, then of the mediators such as prostaglandins, cytokines, and, in recent decades, of the endothelium has com- pleted the concept of the inflammation process. The function of the endothelium appeared to be crucial as a regulator or the initiator of the inflammatory process. Culture of human endothelial cells and experimental systems made it possible to define the molecular basis of inflammation in vascular diseases, in diabetes mellitus, atherosclerosis, vasculitis and thromboembolic complications. Advanced glycation end product receptor (RAGE), present on endothelial cells (ECs) and monocytes, participates in the activation of these cells in inflammatory conditions. Inflammasome is a cytosolic multiprotein that controls the response to diverse microorganisms. It is positively regulated by stimulator of interferon response CGAMP interactor-1 (STING1). Angiogenesis and thrombotic events are dysregulated during inflammation. ECs appear to be a protector, but also a possible initiator of thrombosis. Keywords: endothelial cells; inflammation; inflammasome; angiogenesis; thrombosis; SARS-CoV-2 Citation: Wautier, J.-L.; Wautier, M.-P. 1. Introduction Endothelial Cell Participation in Blood circulation was described by William Harvey in the 17th century (1628 Exercitatio Inflammatory Reaction. Int. J. Mol. Anatomica de Motu Cordis et Sanguinis in Animalibus). Using the microscope, Marcello Sci. 2021, 22, 6341. -
Table S1. 103 Ferroptosis-Related Genes Retrieved from the Genecards
Table S1. 103 ferroptosis-related genes retrieved from the GeneCards. Gene Symbol Description Category GPX4 Glutathione Peroxidase 4 Protein Coding AIFM2 Apoptosis Inducing Factor Mitochondria Associated 2 Protein Coding TP53 Tumor Protein P53 Protein Coding ACSL4 Acyl-CoA Synthetase Long Chain Family Member 4 Protein Coding SLC7A11 Solute Carrier Family 7 Member 11 Protein Coding VDAC2 Voltage Dependent Anion Channel 2 Protein Coding VDAC3 Voltage Dependent Anion Channel 3 Protein Coding ATG5 Autophagy Related 5 Protein Coding ATG7 Autophagy Related 7 Protein Coding NCOA4 Nuclear Receptor Coactivator 4 Protein Coding HMOX1 Heme Oxygenase 1 Protein Coding SLC3A2 Solute Carrier Family 3 Member 2 Protein Coding ALOX15 Arachidonate 15-Lipoxygenase Protein Coding BECN1 Beclin 1 Protein Coding PRKAA1 Protein Kinase AMP-Activated Catalytic Subunit Alpha 1 Protein Coding SAT1 Spermidine/Spermine N1-Acetyltransferase 1 Protein Coding NF2 Neurofibromin 2 Protein Coding YAP1 Yes1 Associated Transcriptional Regulator Protein Coding FTH1 Ferritin Heavy Chain 1 Protein Coding TF Transferrin Protein Coding TFRC Transferrin Receptor Protein Coding FTL Ferritin Light Chain Protein Coding CYBB Cytochrome B-245 Beta Chain Protein Coding GSS Glutathione Synthetase Protein Coding CP Ceruloplasmin Protein Coding PRNP Prion Protein Protein Coding SLC11A2 Solute Carrier Family 11 Member 2 Protein Coding SLC40A1 Solute Carrier Family 40 Member 1 Protein Coding STEAP3 STEAP3 Metalloreductase Protein Coding ACSL1 Acyl-CoA Synthetase Long Chain Family Member 1 Protein