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Molecular Mechanisms and Therapy of Cardiomyopathy
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Molecular Mechanisms and Therapy of 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: 20 February 2025 | Viewed by 2760

Special Issue Editor

Dr. Maicon Landim-Vieira

E-Mail Website
Guest Editor
Biomedical Sciences, Florida State University, Tallahassee, FL 32306, USA
Interests: cardiomyopathies; troponin

Special Issue Information

Dear Colleagues,

Cardiovascular disease is the leading cause of morbidity and mortality globally. Its prevalence necessitates a detailed understanding of the molecular mechanisms underlying cardiomyopathy to develop targeted therapeutic strategies. Several molecular aberrations have been described in cardiomyopathies of all etiologies, including changes in cardiac contractility and morphology, vascular/endothelial dysfunction, mitochondrial and metabolic dysfunction, ischemia/reduced oxygen perfusion, immune cell dysfunction, and epigenetic mechanisms. These molecular mechanisms have yielded several pharmacological treatment strategies for cardiomyopathies of all etiologies. In addition to pharmacological interventions, lifestyle modification (e.g., nutrition/exercise) is now recommended for patients with cardiomyopathy, and several studies have identified molecular changes from such interventions. Thus, investigating the complex molecular aspects of cardiomyopathies is fundamental for identifying the key signaling pathways, genetic and epigenetic factors, and cellular processes that drive disease progression. Improving our knowledge of the mechanistic basis of cardiomyopathies allows for generating novel therapeutic approaches with the goal of improving patient lives.

This Special Issue is supervised by Dr. Maicon Landim-Vieira, who is assisted by the Guest Editor's Assistant Editor Dr. Ann Centner (Florida State University).

Dr. Maicon Landim-Vieira
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • cardiomyopathy
  • nutrition
  • exercise
  • pharmacology
  • molecular mechanisms

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Published Papers (3 papers)

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Research

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17 pages, 6325 KiB  
Article
Dynamics of the Pre-Powerstroke Myosin Lever Arm and the Effects of Omecamtiv Mecarbil
by Matthew Carter Childers and Michael Regnier
Int. J. Mol. Sci. 2024, 25(19), 10425; https://doi.org/10.3390/ijms251910425 - 27 Sep 2024
Viewed by 640
Abstract
The binding of small molecules to sarcomeric myosin can elicit powerful effects on the chemomechanical cycle, making them effective therapeutics in the clinic and research tools at the benchtop. However, these myotropes can have complex effects that act on different phases of the [...] Read more.
The binding of small molecules to sarcomeric myosin can elicit powerful effects on the chemomechanical cycle, making them effective therapeutics in the clinic and research tools at the benchtop. However, these myotropes can have complex effects that act on different phases of the crossbridge cycle and which depend on structural, dynamic, and environmental variables. While small molecule binding sites have been identified crystallographically and their effects on contraction studied extensively, small molecule-induced dynamic changes that link structure–function are less studied. Here, we use molecular dynamics simulations to explore how omecamtiv mecarbil (OM), a cardiac myosin-specific myotrope, alters the coordinated dynamics of the lever arm and the motor domain in the pre-powerstroke state. We show that the lever arm adopts a range of orientations and find that different lever arm orientations are accompanied by changes in the hydrogen bonding patterns near the converter. We find that the binding of OM to myosin reduces the conformational heterogeneity of the lever arm orientation and also adjusts the average lever arm orientation. Finally, we map out the distinct conformations and ligand–protein interactions adopted by OM. These results uncover some structural factors that govern the motor domain–tail orientations and the mechanisms by which OM primes the pre-powerstroke myosin heads. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapy of Cardiomyopathy)
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13 pages, 8056 KiB  
Article
Transcriptomic Alterations in Spliceosome Components in Advanced Heart Failure: Status of Cardiac-Specific Alternative Splicing Factors
by Isaac Giménez-Escamilla, Lorena Pérez-Carrillo, Irene González-Torrent, Marta Delgado-Arija, Carlota Benedicto, Manuel Portolés, Estefanía Tarazón and Esther Roselló-Lletí
Int. J. Mol. Sci. 2024, 25(17), 9590; https://doi.org/10.3390/ijms25179590 - 4 Sep 2024
Viewed by 808
Abstract
Heart failure (HF) is associated with global changes in gene expression. Alternative mRNA splicing (AS) is a key regulatory mechanism underlying these changes. However, the whole status of molecules involved in the splicing process in human HF is unknown. Therefore, we analysed the [...] Read more.
Heart failure (HF) is associated with global changes in gene expression. Alternative mRNA splicing (AS) is a key regulatory mechanism underlying these changes. However, the whole status of molecules involved in the splicing process in human HF is unknown. Therefore, we analysed the spliceosome transcriptome in cardiac tissue (n = 36) from control subjects and HF patients (with ischaemic (ICM) and dilated (DCM) cardiomyopathies) using RNA-seq. We found greater deregulation of spliceosome machinery in ICM. Specifically, we showed widespread upregulation of the E and C complex components, highlighting an increase in SNRPD2 (FC = 1.35, p < 0.05) and DHX35 (FC = 1.34, p < 0.001) mRNA levels. In contrast, we observed generalised downregulation of the A complex and cardiac-specific AS factors, such as the multifunctional protein PCBP2 (FC = −1.29, p < 0.001) and the RNA binding proteins QKI (FC = −1.35, p < 0.01). In addition, we found a relationship between SNPRD2 (an E complex component) and the left ventricular mass index in ICM patients (r = 0.779; p < 0.01). On the other hand, we observed the specific underexpression of DDX46 (FC = −1.29), RBM17 (FC = −1.33), SDE2 (FC = −1.35) and RBFOX1 (FC = −1.33), p < 0.05, in DCM patients. Therefore, these aetiology-related alterations may indicate the differential involvement of the splicing process in the development of ICM and DCM. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapy of Cardiomyopathy)
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Review

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25 pages, 1578 KiB  
Review
What Do We Know about Peripartum Cardiomyopathy? Yesterday, Today, Tomorrow
by Ratko Lasica, Milika Asanin, Jovanka Vukmirovic, Lidija Maslac, Lidija Savic, Marija Zdravkovic, Dejan Simeunovic, Marija Polovina, Aleksandra Milosevic, Dragan Matic, Stefan Juricic, Milica Jankovic, Milan Marinkovic and Lazar Djukanovic
Int. J. Mol. Sci. 2024, 25(19), 10559; https://doi.org/10.3390/ijms251910559 - 30 Sep 2024
Viewed by 755
Abstract
Peripartum cardiomyopathy is a disease that occurs during or after pregnancy and leads to a significant decline in cardiac function in previously healthy women. Peripartum cardiomyopathy has a varying prevalence among women depending on the part of the world where they live, but [...] Read more.
Peripartum cardiomyopathy is a disease that occurs during or after pregnancy and leads to a significant decline in cardiac function in previously healthy women. Peripartum cardiomyopathy has a varying prevalence among women depending on the part of the world where they live, but it is associated with a significant mortality and morbidity in this population. Therefore, timely diagnosis, treatment, and monitoring of this disease from its onset are of utmost importance. Although many risk factors are associated with the occurrence of peripartum cardiomyopathy, such as conditions of life, age of the woman, nutrient deficiencies, or multiple pregnancies, the exact cause of its onset remains unknown. Advances in research on the genetic associations with cardiomyopathies have provided a wealth of data indicating a possible association with peripartum cardiomyopathy, but due to numerous mutations and data inconsistencies, the exact connection remains unclear. Significant insights into the pathophysiological mechanisms underlying peripartum cardiomyopathy have been provided by the theory of an abnormal 16-kDa prolactin, which may be generated in an oxidative stress environment and lead to vascular and consequently myocardial damage. Recent studies supporting this disease mechanism also include research on the efficacy of bromocriptine (a prolactin synthesis inhibitor) in restoring cardiac function in affected patients. Despite significant progress in the research of this disease, there are still insufficient data on the safety of use of certain drugs treating heart failure during pregnancy and breastfeeding. Considering the metabolic changes that occur in different stages of pregnancy and the postpartum period, determining the correct dosing regimen of medications is of utmost importance not only for better treatment and survival of mothers but also for reducing the risk of toxic effects on the fetus. Full article
(This article belongs to the Special Issue Molecular Mechanisms and Therapy of Cardiomyopathy)
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