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  1. Article ; Online: Novel insight into arrhythmogenic remodeling: a target for reversal.

    Batkai, Sandor / Foinquinos, Ariana

    Hypertension research : official journal of the Japanese Society of Hypertension

    2017  Volume 40, Issue 7, Page(s) 632–634

    MeSH term(s) Arrhythmias, Cardiac ; Humans ; Ventricular Remodeling
    Language English
    Publishing date 2017
    Publishing country England
    Document type Journal Article ; Comment
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/hr.2017.46
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    Zs.A 3898: Show issues Location:
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  2. Article ; Online: Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial.

    Bauersachs, Johann / Solomon, Scott D / Anker, Stefan D / Antorrena-Miranda, Isabel / Batkai, Sandor / Viereck, Janika / Rump, Steffen / Filippatos, Gerasimos / Granzer, Ulrich / Ponikowski, Piotr / de Boer, Rudolf A / Vardeny, Orly / Hauke, Wilfried / Thum, Thomas

    European journal of heart failure

    2024  

    Abstract: Aim: Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, ... ...

    Abstract Aim: Inhibition of microRNA (miR)-132 effectively prevents and reverses adverse cardiac remodelling, making it an attractive heart failure (HF) target. CDR132L, a synthetic antisense oligonucleotide selectively blocking pathologically elevated miR-132, demonstrated beneficial effects on left ventricular (LV) structure and function in relevant preclinical models, and was safe and well tolerated in a Phase 1b study in stable chronic HF patients. Patients with acute myocardial infarction (MI) and subsequent LV dysfunction and remodelling have limited therapeutic options, and may profit from early CDR132L treatment.
    Methods: The HF-REVERT (Phase 2, multicenter, randomized, parallel, 3-arm, placebo-controlled Study to Assess Efficacy and Safety of CDR132L in Patients with Reduced Left Ventricular Ejection Fraction after Myocardial Infarction) evaluates the efficacy and safety of CDR132L in HF patients post-acute MI (n = 280), comparing the effect of 5 and 10 mg/kg CDR132L, administered as three single intravenous doses 28 days apart, in addition to standard of care. Key inclusion criteria are the diagnosis of acute MI, the development of systolic dysfunction (LV ejection fraction ≤45%) and elevated N-terminal pro-B-type natriuretic peptide. The study consists of a 6-month double-blinded treatment period with the primary endpoint LV end-systolic volume index and relevant secondary endpoints, followed by a 6-month open-label observation period.
    Conclusion: The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF.
    Language English
    Publishing date 2024-01-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 1483672-5
    ISSN 1879-0844 ; 1388-9842
    ISSN (online) 1879-0844
    ISSN 1388-9842
    DOI 10.1002/ejhf.3139
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  3. Article: Studying Interactions between 2'-O-Me-Modified Inhibitors and MicroRNAs Utilizing Microscale Thermophoresis.

    Herkt, Markus / Batkai, Sandor / Thum, Thomas

    Molecular therapy. Nucleic acids

    2019  Volume 18, Page(s) 259–268

    Abstract: Besides the acquisition of pharmacokinetic parameters of antisense oligonucleotide microRNA (miRNA) inhibitors, such as measuring in vivo concentration, their pharmacodynamic characteristics are also of interest. An emerging and straightforward method ... ...

    Abstract Besides the acquisition of pharmacokinetic parameters of antisense oligonucleotide microRNA (miRNA) inhibitors, such as measuring in vivo concentration, their pharmacodynamic characteristics are also of interest. An emerging and straightforward method for studying molecular interactions is microscale thermophoresis (MST). This technique makes it possible to study interactions between miRNAs and various oligonucleotide inhibitors, independent of the chemical modifications of the inhibitors or their respective target structure, with very little sample volume required compared to competitive techniques, such as surface plasmon resonance (SPR) and isothermal titration calorimetry (ITC). Interaction studies between these inhibitors and their respective target structures were performed, and they allowed the assessment of binding characteristics and parameters, such as EC
    Language English
    Publishing date 2019-08-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2662631-7
    ISSN 2162-2531
    ISSN 2162-2531
    DOI 10.1016/j.omtn.2019.08.019
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  4. Article: Pharmacokinetic Studies of Antisense Oligonucleotides Using MALDI-TOF Mass Spectrometry.

    Herkt, Markus / Foinquinos, Ariana / Batkai, Sandor / Thum, Thomas / Pich, Andreas

    Frontiers in pharmacology

    2020  Volume 11, Page(s) 220

    Abstract: Cardiac diseases are the most frequent causes of death in industrialized countries. Pathological remodeling of the heart muscle is caused by several etiologies such as prolonged hypertension or injuries that can lead to myocardial infarction and in ... ...

    Abstract Cardiac diseases are the most frequent causes of death in industrialized countries. Pathological remodeling of the heart muscle is caused by several etiologies such as prolonged hypertension or injuries that can lead to myocardial infarction and in serious cases also the death of the patient. The micro-RNA miR-132 has been identified as a master-switch in the development of cardiac hypertrophy and adverse remodeling. In this study, MALDI-TOF mass spectrometry (MS) was utilized to establish a robust and fast method to sensitively detect and accurately quantify anti-microRNA (antimiR) oligonucleotides in blood plasma. An antimiR oligonucleotide isolation protocol containing an ethanol precipitation step with glycogen as oligonucleotide carrier as well as a robust and reproducible MS-analysis procedure has been established. Proteinase K treatment was crucial for releasing antimiR oligonucleotides from plasma- as well as cellular proteins and reducing background derived from biological matrices. AntimiR oligonucleotide detection was achieved from samples of studies in different animal models such as mouse and pig where locked nucleic acids-(LNA)-modified antimiR oligonucleotides have been used to generate pharmacokinetic data.
    Language English
    Publishing date 2020-03-25
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2587355-6
    ISSN 1663-9812
    ISSN 1663-9812
    DOI 10.3389/fphar.2020.00220
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  5. Article ; Online: Correction to: Cannabinoid receptor 2 activation alleviates diabetes-induced cardiac dysfunction, inflammation, oxidative stress, and fibrosis.

    Rajesh, Mohanraj / Mukhopadhyay, Partha / Bátkai, Sándor / Arif, Muhammad / Varga, Zoltán V / Mátyás, Csaba / Paloczi, Janos / Lehocki, Andrea / Haskó, György / Pacher, Pal

    GeroScience

    2022  Volume 44, Issue 3, Page(s) 1743–1745

    Language English
    Publishing date 2022-05-20
    Publishing country Switzerland
    Document type Published Erratum
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-022-00593-5
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  6. Article ; Online: Cannabinoid receptor 2 activation alleviates diabetes-induced cardiac dysfunction, inflammation, oxidative stress, and fibrosis.

    Rajesh, Mohanraj / Mukhopadhyay, Partha / Bátkai, Sándor / Arif, Muhammad / Varga, Zoltán V / Mátyás, Csaba / Paloczi, Janos / Lehocki, Andrea / Haskó, György / Pacher, Pal

    GeroScience

    2022  Volume 44, Issue 3, Page(s) 1727–1741

    Abstract: Diabetes mellitus promotes accelerated cardiovascular aging and inflammation, which in turn facilitate the development of cardiomyopathy/heart failure. High glucose-induced oxidative/nitrative stress, activation of various pro-inflammatory, and cell ... ...

    Abstract Diabetes mellitus promotes accelerated cardiovascular aging and inflammation, which in turn facilitate the development of cardiomyopathy/heart failure. High glucose-induced oxidative/nitrative stress, activation of various pro-inflammatory, and cell death pathways are critical in the initiation and progression of the changes culminating in diabetic cardiomyopathy. Cannabinoid 2 receptor (CB
    MeSH term(s) Animals ; Diabetes Mellitus, Experimental/complications ; Diabetes Mellitus, Experimental/drug therapy ; Diabetic Cardiomyopathies/etiology ; Diabetic Cardiomyopathies/metabolism ; Diabetic Cardiomyopathies/pathology ; Fibrosis ; Inflammation/pathology ; Mice ; Oxidative Stress ; Receptors, Cannabinoid/metabolism ; Receptors, Cannabinoid/therapeutic use
    Chemical Substances Receptors, Cannabinoid
    Language English
    Publishing date 2022-04-22
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Intramural
    ZDB-ID 2886586-8
    ISSN 2509-2723 ; 2509-2715
    ISSN (online) 2509-2723
    ISSN 2509-2715
    DOI 10.1007/s11357-022-00565-9
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  7. Article ; Online: Towards novel theranostic approaches in cardiac transplantation medicine.

    Batkai, Sandor / Thum, Thomas

    European heart journal

    2014  Volume 35, Issue 45, Page(s) 3152–3154

    MeSH term(s) Graft Rejection/diagnosis ; Heart Diseases/surgery ; Heart Transplantation ; Humans ; Male ; MicroRNAs/metabolism
    Chemical Substances MicroRNAs
    Language English
    Publishing date 2014-12-01
    Publishing country England
    Document type Comment ; Editorial
    ZDB-ID 603098-1
    ISSN 1522-9645 ; 0195-668X
    ISSN (online) 1522-9645
    ISSN 0195-668X
    DOI 10.1093/eurheartj/ehu376
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    Zs.MO 640: Show issues

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  8. Article ; Online: MicroRNAs in hypertension: mechanisms and therapeutic targets.

    Bátkai, Sándor / Thum, Thomas

    Current hypertension reports

    2011  Volume 14, Issue 1, Page(s) 79–87

    Abstract: Hypertension is a complex, multifactorial disease, and its development is determined by a combination of genetic susceptibility and environmental factors. Several mechanisms have been implicated in the pathogenesis of hypertension: increased activity of ... ...

    Abstract Hypertension is a complex, multifactorial disease, and its development is determined by a combination of genetic susceptibility and environmental factors. Several mechanisms have been implicated in the pathogenesis of hypertension: increased activity of the sympathetic nervous system, overactivation of the renin-angiotensin aldosterone system (RAAS), dysfunction of vascular endothelium, impaired platelet function, thrombogenesis, vascular smooth muscle and cardiac hypertrophy, and altered angiogenesis. MicroRNAs are short, noncoding nucleotides regulating target messenger RNAs at the post-transcriptional level. MicroRNAs are involved in virtually all biologic processes, including cellular proliferation, apoptosis, and differentiation. Thus, microRNA deregulation often results in impaired cellular function and disease development, so microRNAs have potential therapeutic relevance. Many aspects of the development of essential hypertension at the molecular level are still unknown. The elucidation of these processes regulated by microRNAs and the identification of novel microRNA targets in the pathogenesis of hypertension is a highly valuable and exciting strategy that may eventually led to the development of novel treatment approaches for hypertension. This article reviews the potential role of microRNAs in the mechanisms associated with the development and consequences of hypertension and discusses advances in microRNA-based approaches that may be important in treating hypertension.
    MeSH term(s) Antihypertensive Agents/metabolism ; Antihypertensive Agents/pharmacokinetics ; Biological Availability ; Cell Physiological Phenomena/drug effects ; Drug Discovery/methods ; Drug Discovery/trends ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Endothelium, Vascular/physiopathology ; Forecasting ; Humans ; Hypertension/drug therapy ; Hypertension/metabolism ; Hypertension/physiopathology ; MicroRNAs/metabolism ; MicroRNAs/pharmacokinetics ; Models, Biological ; Muscle, Smooth, Vascular/drug effects ; Muscle, Smooth, Vascular/metabolism ; Muscle, Smooth, Vascular/physiopathology ; Neovascularization, Pathologic/metabolism ; Neovascularization, Pathologic/physiopathology ; Platelet Activation/drug effects ; Renin-Angiotensin System ; Sympathetic Nervous System/metabolism ; Sympathetic Nervous System/physiopathology
    Chemical Substances Antihypertensive Agents ; MicroRNAs
    Language English
    Publishing date 2011-11-04
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Review
    ZDB-ID 2057367-4
    ISSN 1534-3111 ; 1522-6417
    ISSN (online) 1534-3111
    ISSN 1522-6417
    DOI 10.1007/s11906-011-0235-6
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  9. Article ; Online: Identification of Gene Expression Signatures for Phenotype-Specific Drug Targeting of Cardiac Fibrosis.

    Lukovic, Dominika / Hasimbegovic, Ena / Winkler, Johannes / Mester-Tonczar, Julia / Müller-Zlabinger, Katrin / Han, Emilie / Spannbauer, Andreas / Traxler-Weidenauer, Denise / Bergler-Klein, Jutta / Pavo, Noemi / Goliasch, Georg / Batkai, Sandor / Thum, Thomas / Zannad, Faiez / Gyöngyösi, Mariann

    International journal of molecular sciences

    2023  Volume 24, Issue 8

    Abstract: We have designed translational animal models to investigate cardiac profibrotic gene signatures. Domestic pigs were treated with cardiotoxic drugs (doxorubicin, DOX, n = 5 or ... ...

    Abstract We have designed translational animal models to investigate cardiac profibrotic gene signatures. Domestic pigs were treated with cardiotoxic drugs (doxorubicin, DOX, n = 5 or Myocet
    MeSH term(s) Animals ; Transcriptome ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors/pharmacology ; Cardiomyopathies/metabolism ; Heart Failure/pathology ; Cardiotoxicity/pathology ; Doxorubicin/pharmacology ; Phenotype ; Fibrosis ; Drug Delivery Systems ; Myocardium/metabolism ; Disease Models, Animal
    Chemical Substances Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Doxorubicin (80168379AG)
    Language English
    Publishing date 2023-04-18
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms24087461
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  10. Article ; Online: MicroRNAs in right ventricular remodelling.

    Batkai, Sandor / Bär, Christian / Thum, Thomas

    Cardiovascular research

    2017  Volume 113, Issue 12, Page(s) 1433–1440

    Abstract: Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology ... ...

    Abstract Right ventricular (RV) remodelling is a lesser understood process of the chronic, progressive transformation of the RV structure leading to reduced functional capacity and subsequent failure. Besides conditions concerning whole hearts, some pathology selectively affects the RV, leading to a distinct RV-specific clinical phenotype. MicroRNAs have been identified as key regulators of biological processes that drive the progression of chronic diseases. The role of microRNAs in diseases affecting the left ventricle has been studied for many years, however there is still limited information on microRNAs specific to diseases in the right ventricle. Here, we review recently described details on the expression, regulation, and function of microRNAs in the pathological remodelling of the right heart. Recently identified strategies using microRNAs as pharmacological targets or biomarkers will be highlighted. Increasing knowledge of pathogenic microRNAs will finally help improve our understanding of underlying distinct mechanisms and help utilize novel targets or biomarkers to develop treatments for patients suffering from right heart diseases.
    Language English
    Publishing date 2017-10-01
    Publishing country England
    Document type Journal Article
    ZDB-ID 80340-6
    ISSN 1755-3245 ; 0008-6363
    ISSN (online) 1755-3245
    ISSN 0008-6363
    DOI 10.1093/cvr/cvx153
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