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  1. Article ; Online: Innate Immunity in Cardiovascular Diseases—Identification of Novel Molecular Players and Targets

    Wolfgang Poller / Bettina Heidecker / Enrico Ammirati / Andreas W. Kuss / Ana Tzvetkova / Wolfram C. Poller / Carsten Skurk / Arash Haghikia

    Journal of Clinical Medicine, Vol 12, Iss 1, p

    2023  Volume 335

    Abstract: During the past few years, unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects ...

    Abstract During the past few years, unexpected developments have driven studies in the field of clinical immunology. One driver of immense impact was the outbreak of a pandemic caused by the novel virus SARS-CoV-2. Excellent recent reviews address diverse aspects of immunological re-search into cardiovascular diseases. Here, we specifically focus on selected studies taking advantage of advanced state-of-the-art molecular genetic methods ranging from genome-wide epi/transcriptome mapping and variant scanning to optogenetics and chemogenetics. First, we discuss the emerging clinical relevance of advanced diagnostics for cardiovascular diseases, including those associated with COVID-19—with a focus on the role of inflammation in cardiomyopathies and arrhythmias. Second, we consider newly identified immunological interactions at organ and system levels which affect cardiovascular pathogenesis. Thus, studies into immune influences arising from the intestinal system are moving towards therapeutic exploitation. Further, powerful new research tools have enabled novel insight into brain–immune system interactions at unprecedented resolution. This latter line of investigation emphasizes the strength of influence of emotional stress—acting through defined brain regions—upon viral and cardiovascular disorders. Several challenges need to be overcome before the full impact of these far-reaching new findings will hit the clinical arena.
    Keywords cardiovascular diseases ; immunology ; innate immunity ; immunogenetics ; noncoding genome ; RNA interference ; Medicine ; R
    Subject code 616
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Epidemiological Impact of Myocarditis

    Ainoosh Golpour / Dimitri Patriki / Paul J. Hanson / Bruce McManus / Bettina Heidecker

    Journal of Clinical Medicine, Vol 10, Iss 4, p

    2021  Volume 603

    Abstract: Myocarditis is an inflammatory disease of the heart muscle with a wide range of potential etiological factors and consequently varying clinical patterns across the world. In this review, we address the epidemiology of myocarditis. Myocarditis was ... ...

    Abstract Myocarditis is an inflammatory disease of the heart muscle with a wide range of potential etiological factors and consequently varying clinical patterns across the world. In this review, we address the epidemiology of myocarditis. Myocarditis was considered a rare disease until intensified research efforts in recent decades revealed its true epidemiological importance. While it remains a challenge to determine the true prevalence of myocarditis, studies are underway to obtain better approximations of the proportions of this disease. Nowadays, the prevalence of myocarditis has been reported from 10.2 to 105.6 per 100,000 worldwide, and its annual occurrence is estimated at about 1.8 million cases. This wide range of reported cases reflects the uncertainty surrounding the true prevalence and a potential underdiagnosis of this disease. Since myocarditis continues to be a significant public health issue, particularly in young adults in whom myocarditis is among the most common causes of sudden cardiac death, improved diagnostic and therapeutic procedures are necessary. This manuscript aims to summarize the current knowledge on the epidemiology of myocarditis, new diagnostic approaches and the current epidemiological impact of the COVID-19 pandemic.
    Keywords myocarditis ; epidemiology ; incidence and prevalence ; myocarditis associated with COVID-19 ; etiology ; diagnosis ; Medicine ; R
    Subject code 610
    Language English
    Publishing date 2021-02-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: FIMICS

    Huseyin Firat / Lu Zhang / Shounak Baksi / Przemyslaw Leszek / Eric Schordan / Samir Ounzain / Jan Kottwitz / Dimitri Patriki / Bettina Heidecker / Thomas F. Lüscher / Thierry Pedrazzini / Yvan Devaux

    Heliyon, Vol 9, Iss 1, Pp e13087- (2023)

    A panel of long noncoding RNAs for cardiovascular conditions

    2023  

    Abstract: Summary: Cardiovascular disorders such as heart failure are leading causes of mortality. Patient stratification via identification of novel biomarkers could improve management of cardiovascular diseases of complex etiologies. Long-noncoding RNAs (lncRNAs) ...

    Abstract Summary: Cardiovascular disorders such as heart failure are leading causes of mortality. Patient stratification via identification of novel biomarkers could improve management of cardiovascular diseases of complex etiologies. Long-noncoding RNAs (lncRNAs) are highly tissue-specific in nature and have emerged as important biomarkers in human diseases. In this study, we aimed to identify cardiac-enriched lncRNAs as potential biomarkers for cardiovascular conditions.Deep RNA sequencing and quantitative PCR identified differentially expressed lncRNAs between failing and non-failing hearts. An independent dataset was used to evaluate the enrichment of lncRNAs in normal hearts.We identified a panel of 2906 lncRNAs, named FIMICS, that were either cardiac-enriched or differentially expressed between failing and non-failing hearts. Expression of lncRNAs in blood samples differentiated patients with myocarditis and acute myocardial infarction.We hereby present the FIMICS panel, a readily available tool to provide insights into cardiovascular pathologies and which could be helpful for diagnosis, monitoring and prognosis purposes.
    Keywords Biomarker ; Heart failure ; Cardiovascular condition ; Long-noncoding RNA ; Deep RNA sequencing ; Cardiac enriched RNA ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
    Subject code 610
    Language English
    Publishing date 2023-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Highly multiplexed immune repertoire sequencing links multiple lymphocyte classes with severity of response to COVID-19

    Richard Dannebaum / Phillip Suwalski / Hosseinali Asgharian / Gracie Du Zhipei / Hai Lin / January Weiner, 3rd / Manuel Holtgrewe / Charlotte Thibeault / Melina Müller / Xiaomin Wang / Zehra Karadeniz / Jacopo Saccomanno / Jan-Moritz Doehn / Ralf-Harto Hübner / Bernd Hinzmann / Anja Blüher / Sandra Siemann / Dilduz Telman / Norbert Suttorp /
    Martin Witzenrath / Stefan Hippenstiel / Carsten Skurk / Wolfgang Poller / Leif E Sander / Dieter Beule / Florian Kurth / Toumy Guettouche / Ulf Landmesser / Jan Berka / Khai Luong / Florian Rubelt / Bettina Heidecker

    EClinicalMedicine, Vol 48, Iss , Pp 101438- (2022)

    2022  

    Abstract: Summary: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to ...

    Abstract Summary: Background: Disease progression of subjects with coronavirus disease 2019 (COVID-19) varies dramatically. Understanding the various types of immune response to SARS-CoV-2 is critical for better clinical management of coronavirus outbreaks and to potentially improve future therapies. Disease dynamics can be characterized by deciphering the adaptive immune response. Methods: In this cross-sectional study we analyzed 117 peripheral blood immune repertoires from healthy controls and subjects with mild to severe COVID-19 disease to elucidate the interplay between B and T cells. We used an immune repertoire Primer Extension Target Enrichment method (immunoPETE) to sequence simultaneously human leukocyte antigen (HLA) restricted T cell receptor beta chain (TRB) and unrestricted T cell receptor delta chain (TRD) and immunoglobulin heavy chain (IgH) immune receptor repertoires. The distribution was analyzed of TRB, TRD and IgH clones between healthy and COVID-19 infected subjects. Using McFadden's Adjusted R2 variables were examined for a predictive model. The aim of this study is to analyze the influence of the adaptive immune repertoire on the severity of the disease (value on the World Health Organization Clinical Progression Scale) in COVID-19. Findings: Combining clinical metadata with clonotypes of three immune receptor heavy chains (TRB, TRD, and IgH), we found significant associations between COVID-19 disease severity groups and immune receptor sequences of B and T cell compartments. Logistic regression showed an increase in shared IgH clonal types and decrease of TRD in subjects with severe COVID-19. The probability of finding shared clones of TRD clonal types was highest in healthy subjects (controls). Some specific TRB clones seems to be present in severe COVID-19 (Figure S7b). The most informative models (McFadden´s Adjusted R2=0.141) linked disease severity with immune repertoire measures across all three cell types, as well as receptor-specific cell counts, highlighting the importance of multiple ...
    Keywords COVID-19 ; Immune repertoires ; Immune receptor ; Clinical course ; Medicine (General) ; R5-920
    Subject code 610 ; 616
    Language English
    Publishing date 2022-06-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Structured, Harmonized, and Interoperable Integration of Clinical Routine Data to Compute Heart Failure Risk Scores

    Kim K. Sommer / Ali Amr / Udo Bavendiek / Felix Beierle / Peter Brunecker / Henning Dathe / Jürgen Eils / Maximilian Ertl / Georg Fette / Matthias Gietzelt / Bettina Heidecker / Kristian Hellenkamp / Peter Heuschmann / Jennifer D. E. Hoos / Tibor Kesztyüs / Fabian Kerwagen / Aljoscha Kindermann / Dagmar Krefting / Ulf Landmesser /
    Michael Marschollek / Benjamin Meder / Angela Merzweiler / Fabian Prasser / Rüdiger Pryss / Jendrik Richter / Philipp Schneider / Stefan Störk / Christoph Dieterich

    Life, Vol 12, Iss 749, p

    2022  Volume 749

    Abstract: Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled ... ...

    Abstract Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.
    Keywords medical informatics initiative ; HiGHmed ; medical data integration center ; clinical routine data ; heart failure ; risk prediction scores ; Science ; Q
    Subject code 310
    Language English
    Publishing date 2022-05-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: tRNA-like Transcripts from the NEAT1-MALAT1 Genomic Region Critically Influence Human Innate Immunity and Macrophage Functions

    Martina Gast / Vanasa Nageswaran / Andreas W. Kuss / Ana Tzvetkova / Xiaomin Wang / Liliana H. Mochmann / Pegah Ramezani Rad / Stefan Weiss / Stefan Simm / Tanja Zeller / Henry Voelzke / Wolfgang Hoffmann / Uwe Völker / Stefan B. Felix / Marcus Dörr / Antje Beling / Carsten Skurk / David-Manuel Leistner / Bernhard H. Rauch /
    Tetsuro Hirose / Bettina Heidecker / Karin Klingel / Shinichi Nakagawa / Wolfram C. Poller / Filip K. Swirski / Arash Haghikia / Wolfgang Poller

    Cells, Vol 11, Iss 3970, p

    2022  Volume 3970

    Abstract: The evolutionary conserved NEAT1-MALAT1 gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. Whereas functions have ... ...

    Abstract The evolutionary conserved NEAT1-MALAT1 gene cluster generates large noncoding transcripts remaining nuclear, while tRNA-like transcripts (mascRNA, menRNA) enzymatically generated from these precursors translocate to the cytosol. Whereas functions have been assigned to the nuclear transcripts, data on biological functions of the small cytosolic transcripts are sparse. We previously found NEAT1 −/− and MALAT1 −/− mice to display massive atherosclerosis and vascular inflammation. Here, employing selective targeted disruption of menRNA or mascRNA, we investigate the tRNA-like molecules as critical components of innate immunity. CRISPR-generated human ΔmascRNA and ΔmenRNA monocytes/macrophages display defective innate immune sensing, loss of cytokine control, imbalance of growth/angiogenic factor expression impacting upon angiogenesis, and altered cell–cell interaction systems. Antiviral response, foam cell formation/oxLDL uptake, and M1/M2 polarization are defective in ΔmascRNA/ΔmenRNA macrophages, defining first biological functions of menRNA and describing new functions of mascRNA. menRNA and mascRNA represent novel components of innate immunity arising from the noncoding genome. They appear as prototypes of a new class of noncoding RNAs distinct from others (miRNAs, siRNAs) by biosynthetic pathway and intracellular kinetics. Their NEAT1-MALAT1 region of origin appears as archetype of a functionally highly integrated RNA processing system.
    Keywords immunology ; innate immunity ; immunogenetics ; noncoding genome ; tRNA biology ; evolutionary genetics ; Cytology ; QH573-671
    Subject code 572
    Language English
    Publishing date 2022-12-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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