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From Bench to Bedside: Comprehensive Research on Cardiomyopathy

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (15 April 2024) | Viewed by 7224

Special Issue Editor


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Guest Editor
The Heart and Vascular Center, Semmelweis University, H-1122 Budapest, Hungary
Interests: cardiomyopathy; heart failure; diagnosis; treatment; ischemic heart disease; myocardial remodeling; reverse remodeling

Special Issue Information

Dear Colleagues,

Despite of the significant advances in the management of chronic heart failure (CHF), the continuing high prevalence of this condition coupled with high mortality rate and poor quality of life warrants further therapeutical improvements. It is worth to mention that a wide spectrum of pathological conditions with different underlying subcellular alterations (including primary cardiomyopathies with genetic backgrounds as well as secondary cardiomyopathies due to ischemic, hemodynamic or toxic insults) could lead to the development of CHF. Despite of the significantly different molecular background, a similar pharmacological treatment has been applied in distinct cardiomyopathies. However, it has been increasingly recognized that a deeper understanding of the responsible cell signaling pathways and key molecular alterations in different cardiac pathologies could promote the development of more specific pharmacological agents Furthermore, there is an unmet medical need for the identification of novel biomarkers (either circulating molecular factors or cardiac imaging patterns), which could not only facilitate the in time diagnosis of CHF but also help to monitor the progression of the disease.

The Special Issue “From Bench to Bedside: Molecular and Translational Research on Cardiomyopathy” aims to uncover novel findings in relation to distinct forms of primary and secondary cardiomyopathies. For this call, we invite fundamental experimental (including ex vivo and in vivo approaches), translational as well as clinical research that uncover novel findings in the pathophysiology and treatment of CHF with distinct etiologies. We are especially interested in submissions focused on the following:

  • Improving our understanding of the specific molecular and cellular alterations in distinct forms of cardiomyopathies
  • Exploring novel pharmacological/non-pharmacological therapies for CHF with different etiologies
  • Evaluating novel biomarkers (either by different imaging tools [e.g. echocardiography, CT] or serum/plasma factors), which could facilitate the diagnosis of cardiomyopathies.

Dr. Mihály Ruppert
Guest Editor

Manuscript Submission Information

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Keywords

  • cardiomyopathy
  • chronic heart failure
  • pathological remodeling
  • left ventricular hypertrophy
  • right heart failure
  • echocardiography
  • cell signaling

Published Papers (3 papers)

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Research

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18 pages, 4573 KiB  
Article
Droplet Digital PCR Is a Novel Screening Method Identifying Potential Cardiac G-Protein-Coupled Receptors as Candidate Pharmacological Targets in a Rat Model of Pressure-Overload-Induced Cardiac Dysfunction
by Nabil V. Sayour, Viktória É. Tóth, Regina N. Nagy, Imre Vörös, Tamás G. Gergely, Zsófia Onódi, Noémi Nagy, Csaba Bödör, Barnabás Váradi, Mihály Ruppert, Tamás Radovits, Federico Bleckwedel, Laura C. Zelarayán, Pal Pacher, Bence Ágg, Anikó Görbe, Péter Ferdinandy and Zoltán V. Varga
Int. J. Mol. Sci. 2023, 24(18), 13826; https://doi.org/10.3390/ijms241813826 - 7 Sep 2023
Cited by 2 | Viewed by 1612
Abstract
The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the [...] Read more.
The identification of novel drug targets is needed to improve the outcomes of heart failure (HF). G-protein-coupled receptors (GPCRs) represent the largest family of targets for already approved drugs, thus providing an opportunity for drug repurposing. Here, we aimed (i) to investigate the differential expressions of 288 cardiac GPCRs via droplet digital PCR (ddPCR) and bulk RNA sequencing (RNAseq) in a rat model of left ventricular pressure-overload; (ii) to compare RNAseq findings with those of ddPCR; and (iii) to screen and test for novel, translatable GPCR drug targets in HF. Male Wistar rats subjected to transverse aortic constriction (TAC, n = 5) showed significant systolic dysfunction vs. sham operated animals (SHAM, n = 5) via echocardiography. In TAC vs. SHAM hearts, RNAseq identified 69, and ddPCR identified 27 significantly differentially expressed GPCR mRNAs, 8 of which were identified using both methods, thus showing a correlation between the two methods. Of these, Prostaglandin-F2α-receptor (Ptgfr) was further investigated and localized on cardiomyocytes and fibroblasts in murine hearts via RNA-Scope. Antagonizing Ptgfr via AL-8810 reverted angiotensin-II-induced cardiomyocyte hypertrophy in vitro. In conclusion, using ddPCR as a novel screening method, we were able to identify GPCR targets in HF. We also show that the antagonism of Ptgfr could be a novel target in HF by alleviating cardiomyocyte hypertrophy. Full article
(This article belongs to the Special Issue From Bench to Bedside: Comprehensive Research on Cardiomyopathy)
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14 pages, 12648 KiB  
Article
Inflammasome Activity in the Skeletal Muscle and Heart of Rodent Models for Duchenne Muscular Dystrophy
by Zsófia Onódi, Petra Lujza Szabó, Dániel Kucsera, Péter Pokreisz, Christopher Dostal, Karlheinz Hilber, Gavin Y. Oudit, Bruno K. Podesser, Péter Ferdinandy, Zoltán V. Varga and Attila Kiss
Int. J. Mol. Sci. 2023, 24(10), 8497; https://doi.org/10.3390/ijms24108497 - 9 May 2023
Cited by 2 | Viewed by 2168
Abstract
Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. [...] Read more.
Duchenne muscular dystrophy (DMD) is characterized by wasting of muscles that leads to difficulty moving and premature death, mainly from heart failure. Glucocorticoids are applied in the management of the disease, supporting the hypothesis that inflammation may be driver as well as target. However, the inflammatory mechanisms during progression of cardiac and skeletal muscle dysfunction are still not well characterized. Our objective was to characterize the inflammasomes in myocardial and skeletal muscle in rodent models of DMD. Gastrocnemius and heart samples were collected from mdx mice and DMDmdx rats (3 and 9–10 months). Inflammasome sensors and effectors were assessed by immunoblotting. Histology was used to assess leukocyte infiltration and fibrosis. In gastrocnemius, a tendency towards elevation of gasdermin D irrespective of the age of the animal was observed. The adaptor protein was elevated in the mdx mouse skeletal muscle and heart. Increased cleavage of the cytokines was observed in the skeletal muscle of the DMDmdx rats. Sensor or cytokine expression was not changed in the tissue samples of the mdx mice. In conclusion, inflammatory responses are distinct between the skeletal muscle and heart in relevant models of DMD. Inflammation tends to decrease over time, supporting the clinical observations that the efficacy of anti-inflammatory therapies might be more prominent in the early stage. Full article
(This article belongs to the Special Issue From Bench to Bedside: Comprehensive Research on Cardiomyopathy)
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Review

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12 pages, 1495 KiB  
Review
The Role of MicroRNAs in Myocarditis—What Can We Learn from Clinical Trials?
by Olga Grodzka, Grzegorz Procyk and Aleksandra Gąsecka
Int. J. Mol. Sci. 2022, 23(24), 16022; https://doi.org/10.3390/ijms232416022 - 16 Dec 2022
Cited by 7 | Viewed by 2819
Abstract
Myocarditis is an inflammatory disease of the heart with a viral infection as the most common cause. It affects most commonly young adults. Although endomyocardial biopsy and cardiac magnetic resonance are used in the diagnosis, neither of them demonstrates all the required qualities. [...] Read more.
Myocarditis is an inflammatory disease of the heart with a viral infection as the most common cause. It affects most commonly young adults. Although endomyocardial biopsy and cardiac magnetic resonance are used in the diagnosis, neither of them demonstrates all the required qualities. There is a clear need for a non-invasive, generally available diagnostic tool that will still remain highly specific and sensitive. These requirements could be possibly met by microribonucleic acids (miRNAs), which are small, non-coding RNA molecules that regulate many fundamental cell functions. They can be isolated from cells, tissues, or body fluids. Recently, several clinical studies have shown the deregulation of different miRNAs in myocarditis. The phase of the disease has also been evidenced to influence miRNA levels. These changes have been observed both in adult and pediatric patients. Some studies have revealed a correlation between the change in particular miRNA concentration and the degree of cardiac damage and inflammation. All of this indicates miRNAs as potential novel biomarkers in the diagnosis of myocarditis, as well as a prognostic tool for this condition. This review aims to summarize the current knowledge about the role of miRNAs in myocarditis based on the results of clinical studies. Full article
(This article belongs to the Special Issue From Bench to Bedside: Comprehensive Research on Cardiomyopathy)
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