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  1. Article ; Online: Disease Models & Mechanisms in the Age of Big Data.

    Hatzopoulos, Antonis K

    Disease models & mechanisms

    2019  Volume 12, Issue 8

    Abstract: In the decade since Disease Models & Mechanisms was launched, the emergence of Big Data as the main foundation of biological information is having a profound effect on how we do research and it has provoked some interesting questions. Is Big Data ... ...

    Abstract In the decade since Disease Models & Mechanisms was launched, the emergence of Big Data as the main foundation of biological information is having a profound effect on how we do research and it has provoked some interesting questions. Is Big Data exploration replacing hypothesis-driven basic research? And, to what extent is disease modeling in the laboratory still relevant to medical research? Recent examples of synergistic approaches utilizing animal modeling and electronic medical records mining show that combining efforts between disease models and clinical datasets can uncover not only disease etiologies, but also novel molecular and cellular mechanisms linked to gene function.
    MeSH term(s) Animals ; Big Data ; Disease Models, Animal ; Periodicals as Topic ; Phenotype
    Language English
    Publishing date 2019-08-20
    Publishing country England
    Document type Editorial ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1754-8411
    ISSN (online) 1754-8411
    DOI 10.1242/dmm.041699
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Bone morphogenetic protein signaling in inflammation.

    Wu, David H / Hatzopoulos, Antonis K

    Experimental biology and medicine (Maywood, N.J.)

    2019  Volume 244, Issue 2, Page(s) 147–156

    Abstract: Impact statement: By compiling findings from recent studies, this review will garner novel insight on the dynamic and complex role of BMP signaling in diseases of inflammation, highlighting the specific roles played by both individual ligands and ... ...

    Abstract Impact statement: By compiling findings from recent studies, this review will garner novel insight on the dynamic and complex role of BMP signaling in diseases of inflammation, highlighting the specific roles played by both individual ligands and endogenous antagonists. Ultimately, this summary will help inform the high therapeutic value of targeting this pathway for modulating diseases of inflammation.
    MeSH term(s) Anemia/metabolism ; Anemia/physiopathology ; Arthritis/metabolism ; Arthritis/physiopathology ; Bone Morphogenetic Proteins/metabolism ; Bone Morphogenetic Proteins/physiology ; Embryonic Development ; Fibrosis/metabolism ; Humans ; Inflammation/metabolism ; Myocardial Infarction/metabolism ; Myocardial Infarction/physiopathology ; Signal Transduction ; Vascular Calcification/metabolism
    Chemical Substances Bone Morphogenetic Proteins
    Language English
    Publishing date 2019-02-07
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 4015-0
    ISSN 1535-3699 ; 1525-1373 ; 0037-9727
    ISSN (online) 1535-3699 ; 1525-1373
    ISSN 0037-9727
    DOI 10.1177/1535370219828694
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Transcriptome analysis of cardiac endothelial cells after myocardial infarction reveals temporal changes and long-term deficits.

    Basu, Chitra / Cannon, Presley L / Awgulewitsch, Cassandra P / Galindo, Cristi L / Gamazon, Eric R / Hatzopoulos, Antonis K

    Scientific reports

    2024  Volume 14, Issue 1, Page(s) 9991

    Abstract: Endothelial cells (ECs) have essential roles in cardiac tissue repair after myocardial infarction (MI). To establish stage-specific and long-term effects of the ischemic injury on cardiac ECs, we analyzed their transcriptome at landmark time points after ...

    Abstract Endothelial cells (ECs) have essential roles in cardiac tissue repair after myocardial infarction (MI). To establish stage-specific and long-term effects of the ischemic injury on cardiac ECs, we analyzed their transcriptome at landmark time points after MI in mice. We found that early EC response at Day 2 post-MI centered on metabolic changes, acquisition of proinflammatory phenotypes, initiation of the S phase of cell cycle, and activation of stress-response pathways, followed by progression to mitosis (M/G2 phase) and acquisition of proangiogenic and mesenchymal properties during scar formation at Day 7. In contrast, genes involved in vascular physiology and maintenance of vascular tone were suppressed. Importantly, ECs did not return to pre-injury phenotypes after repair has been completed but maintained inflammatory, fibrotic and thrombotic characteristics and lost circadian rhythmicity. We discovered that the highest induced transcript is the mammalian-specific Sh2d5 gene that promoted migration and invasion of ECs through Rac1 GTPase. Our results revealed a synchronized, temporal activation of disease phenotypes, metabolic pathways, and proliferation in quiescent ECs after MI, indicating that precisely-timed interventions are necessary to optimize cardiac tissue repair and improve outcomes. Furthermore, long-term effects of acute ischemic injury on ECs may contribute to vascular dysfunction and development of heart failure.
    MeSH term(s) Animals ; Myocardial Infarction/genetics ; Myocardial Infarction/metabolism ; Myocardial Infarction/pathology ; Mice ; Endothelial Cells/metabolism ; Endothelial Cells/pathology ; Gene Expression Profiling ; Transcriptome ; Male ; Mice, Inbred C57BL ; Myocardium/metabolism ; Myocardium/pathology ; rac1 GTP-Binding Protein/metabolism ; rac1 GTP-Binding Protein/genetics ; Disease Models, Animal ; Cell Proliferation ; Cell Movement/genetics
    Chemical Substances rac1 GTP-Binding Protein (EC 3.6.5.2)
    Language English
    Publishing date 2024-05-01
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2615211-3
    ISSN 2045-2322 ; 2045-2322
    ISSN (online) 2045-2322
    ISSN 2045-2322
    DOI 10.1038/s41598-024-59155-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Differentiation of Atrial Cardiomyocytes from Pluripotent Stem Cells Using the BMP Antagonist Grem2.

    Bylund, Jeffery B / Hatzopoulos, Antonis K

    Journal of visualized experiments : JoVE

    2016  , Issue 109

    Abstract: Protocols for generating populations of cardiomyocytes from pluripotent stem cells have been developed, but these generally yield cells of mixed phenotypes. Researchers interested in pursuing studies involving specific myocyte subtypes require a more ... ...

    Abstract Protocols for generating populations of cardiomyocytes from pluripotent stem cells have been developed, but these generally yield cells of mixed phenotypes. Researchers interested in pursuing studies involving specific myocyte subtypes require a more directed differentiation approach. By treating mouse embryonic stem (ES) cells with Grem2, a secreted BMP antagonist that is necessary for atrial chamber formation in vivo, a large number of cardiac cells with an atrial phenotype can be generated. Use of the engineered Myh6-DSRed-Nuc pluripotent stem cell line allows for identification, selection, and purification of cardiomyocytes. In this protocol embryoid bodies are generated from Myh6-DSRed-Nuc cells using the hanging drop method and kept in suspension until differentiation day 4 (d4). At d4 cells are treated with Grem2 and plated onto gelatin coated plates. Between d8-d10 large contracting areas are observed in the cultures and continue to expand and mature through d14. Molecular, histological and electrophysiogical analyses indicate cells in Grem2-treated cells acquire atrial-like characteristics providing an in vitro model to study the biology of atrial cardiomyocytes and their response to various pharmacological agents.
    MeSH term(s) Animals ; Cell Differentiation ; Cellular Reprogramming Techniques/methods ; Cytokines ; Heart Atria/cytology ; Mice ; Myocytes, Cardiac/cytology ; Myocytes, Cardiac/drug effects ; Pluripotent Stem Cells/cytology ; Pluripotent Stem Cells/drug effects ; Proteins/pharmacology
    Chemical Substances Cytokines ; Grem2 protein, mouse ; Proteins
    Language English
    Publishing date 2016-03-10
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Video-Audio Media
    ZDB-ID 2259946-0
    ISSN 1940-087X ; 1940-087X
    ISSN (online) 1940-087X
    ISSN 1940-087X
    DOI 10.3791/53919
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and Disease.

    Awgulewitsch, Cassandra P / Trinh, Linh T / Hatzopoulos, Antonis K

    Current cardiology reports

    2017  Volume 19, Issue 6, Page(s) 51

    Abstract: Purpose of review: This review aims to summarize recent findings regarding the plasticity and fate switching among somatic and progenitor cells residing in the vascular wall of blood vessels in health and disease.: Recent findings: Cell lineage ... ...

    Abstract Purpose of review: This review aims to summarize recent findings regarding the plasticity and fate switching among somatic and progenitor cells residing in the vascular wall of blood vessels in health and disease.
    Recent findings: Cell lineage tracing methods have identified multiple origins of stem cells, macrophages, and matrix-producing cells that become mobilized after acute or chronic injury of cardiovascular tissues. These studies also revealed that in the disease environment, resident somatic cells become plastic, thereby changing their stereotypical identities to adopt proinflammatory and profibrotic phenotypes. Currently, the functional significance of this heterogeneity among reparative cells is unknown. Furthermore, mechanisms that control cellular plasticity and fate decisions in the disease environment are poorly understood. Cardiovascular diseases are responsible for the majority of deaths worldwide. From a therapeutic perspective, these novel discoveries may identify new targets to improve the repair and regeneration of the cardiovascular system.
    MeSH term(s) Blood Vessels/cytology ; Blood Vessels/physiology ; Cardiovascular Diseases/therapy ; Cell Differentiation ; Cell Lineage ; Cell Plasticity ; Epithelial-Mesenchymal Transition ; Homeostasis ; Humans ; Stem Cells/cytology ; Stem Cells/physiology
    Language English
    Publishing date 2017-04-21
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 2055373-0
    ISSN 1534-3170 ; 1523-3782
    ISSN (online) 1534-3170
    ISSN 1523-3782
    DOI 10.1007/s11886-017-0861-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Differentiation of atrial cardiomyocytes from pluripotent stem cells using the bmp antagonist grem2

    Bylund, Jeffery B / Hatzopoulos, Antonis K

    Journal of visualized experiments. 2016 Mar. 10, , no. 109

    2016  

    Abstract: Protocols for generating populations of cardiomyocytes from pluripotent stem cells have been developed, but these generally yield cells of mixed phenotypes. Researchers interested in pursuing studies involving specific myocyte subtypes require a more ... ...

    Abstract Protocols for generating populations of cardiomyocytes from pluripotent stem cells have been developed, but these generally yield cells of mixed phenotypes. Researchers interested in pursuing studies involving specific myocyte subtypes require a more directed differentiation approach. By treating mouse embryonic stem (ES) cells with Grem2, a secreted BMP antagonist that is necessary for atrial chamber formation in vivo, a large number of cardiac cells with an atrial phenotype can be generated. Use of the engineered Myh6-DSRed-Nuc pluripotent stem cell line allows for identification, selection, and purification of cardiomyocytes. In this protocol embryoid bodies are generated from Myh6-DSRed-Nuc cells using the hanging drop method and kept in suspension until differentiation day 4 (d4). At d4 cells are treated with Grem2 and plated onto gelatin coated plates. Between d8-d10 large contracting areas are observed in the cultures and continue to expand and mature through d14. Molecular, histological and electrophysiogical analyses indicate cells in Grem2-treated cells acquire atrial-like characteristics providing an in vitro model to study the biology of atrial cardiomyocytes and their response to various pharmacological agents.
    Keywords antagonists ; cardiomyocytes ; cell lines ; gelatin ; histology ; mice ; models ; phenotype ; stem cells
    Language English
    Dates of publication 2016-0310
    Size p. e53919.
    Publishing place Journal of Visualized Experiments
    Document type Article
    ZDB-ID 2259946-0
    ISSN 1940-087X
    ISSN 1940-087X
    DOI 10.3791/53919
    Database NAL-Catalogue (AGRICOLA)

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  7. Article ; Online: Pharmacological modulation of prostaglandin E

    Bosma, Karin J / Ghosh, Monica / Andrei, Spencer R / Zhong, Lin / Dunn, Jennifer C / Ricciardi, Valerie F / Burkett, Juliann B / Hatzopoulos, Antonis K / Damron, Derek S / Gannon, Maureen

    Physiological reports

    2022  Volume 10, Issue 7, Page(s) e15212

    Abstract: Type 2 diabetes (T2D) affects >30 million Americans and nearly 70% of individuals with T2D will die from cardiovascular disease (CVD). Circulating levels of the inflammatory signaling lipid, prostaglandin ... ...

    Abstract Type 2 diabetes (T2D) affects >30 million Americans and nearly 70% of individuals with T2D will die from cardiovascular disease (CVD). Circulating levels of the inflammatory signaling lipid, prostaglandin E
    MeSH term(s) Animals ; Diabetes Mellitus, Type 2/drug therapy ; Dinoprostone/pharmacology ; Humans ; Hyperglycemia ; Mice ; Myocytes, Cardiac ; Receptors, Prostaglandin E, EP3 Subtype ; Receptors, Prostaglandin E, EP4 Subtype
    Chemical Substances Receptors, Prostaglandin E, EP3 Subtype ; Receptors, Prostaglandin E, EP4 Subtype ; Dinoprostone (K7Q1JQR04M)
    Language English
    Publishing date 2022-04-11
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2724325-4
    ISSN 2051-817X ; 2051-817X
    ISSN (online) 2051-817X
    ISSN 2051-817X
    DOI 10.14814/phy2.15212
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Time is like a clock in my heart: implications for stem cell delivery after myocardial infarction.

    Schoenhard, John A / Hatzopoulos, Antonis K

    Cardiology

    2010  Volume 117, Issue 2, Page(s) 158–160

    MeSH term(s) Hematopoietic Stem Cell Mobilization ; Humans ; Myocardial Infarction/therapy ; Time Factors
    Language English
    Publishing date 2010-10-30
    Publishing country Switzerland
    Document type Editorial ; Research Support, N.I.H., Extramural
    ZDB-ID 80092-2
    ISSN 1421-9751 ; 0008-6312
    ISSN (online) 1421-9751
    ISSN 0008-6312
    DOI 10.1159/000321396
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Book: Molecular mechanisms of blood vessel growth in health and disease

    Hatzopoulos, Antonis K

    final report

    2004  

    Institution GSF-Forschungszentrum für Umwelt und Gesundheit
    Author's details Institute for Clinical Molecular Biology & Tumor Genetics, GSF-Research Center for Environment & Health. Principal investigator: Antonis K. Hatzopoulos
    Language English ; German
    Size [6] Bl.
    Publishing place München
    Document type Book
    Note Mit dt. Zsfassung ; Förderkennzeichen BMBF 01KW9907
    Database Library catalogue of the German National Library of Science and Technology (TIB), Hannover

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  10. Article ; Online: Stem cell therapy for cardiac repair: benefits and barriers.

    Joggerst, Steven J / Hatzopoulos, Antonis K

    Expert reviews in molecular medicine

    2009  Volume 11, Page(s) e20

    Abstract: Cardiovascular disease remains the leading cause of death worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies aim largely to attenuate the pathological ... ...

    Abstract Cardiovascular disease remains the leading cause of death worldwide. Acute ischaemic injury and chronic cardiomyopathies lead to permanent loss of cardiac tissue and ultimately heart failure. Current therapies aim largely to attenuate the pathological remodelling that occurs after injury and to reduce risk factors for cardiovascular disease. Studies in animal models indicate that transplantation of mesenchymal stem cells, bone-marrow-derived haematopoietic stem cells, skeletal myoblasts, or embryonic stem cells has the potential to improve the function of ventricular muscle after ischaemic injury. Clinical trials using primarily bone-marrow-derived cells and skeletal myoblasts have also produced some encouraging results. However, the current experimental evidence suggests that the benefits of cell therapy are modest, the generation of new cardiac tissue is low, and the predominant mechanisms of action of transplanted stem cells involve favourable paracrine effects on injured myocardium. Recent studies show that the adult heart possesses various pools of putative resident stem cells, raising the hope that these cells can be isolated for therapy or manipulated in vivo to improve the healing of cardiac muscle after injury. This article reviews the properties and potential of the various stem cell populations for cardiac repair and regeneration as well as the barriers that might lie ahead.
    MeSH term(s) Animals ; Bone Marrow Transplantation/methods ; Cardiovascular Diseases/therapy ; Embryonic Stem Cells/transplantation ; Humans ; Myocardial Infarction/therapy ; Stem Cell Transplantation/methods
    Language English
    Publishing date 2009-07-08
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ISSN 1462-3994
    ISSN (online) 1462-3994
    DOI 10.1017/S1462399409001124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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