Special Issue "Cardiomyopathy at the Sub-Cellular Level"

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425).

Deadline for manuscript submissions: closed (31 March 2021).

Special Issue Editor

Dr. James Smyth
E-Mail Website
Guest Editor
Virginia Tech Carilion Researc Institute, Roanoke, VA 24016, USA
Interests: cardiomyopathy; gap junction; connexin; translation; trafficking; intercalated disc; virology

Special Issue Information

Dear Colleagues,

This Special Issue of JCDD is focused on “Cardiomyopathy at the Sub-Cellular Level”, encompassing the molecular mechanisms of pathological remodeling within cardiomyocytes that lead to mechanical and electrical perturbation of the heart. Critical cardiomyocyte structures and nano-domains effect efficient excitation-contraction coupling (e.g., T-tubules, diads, sarcomere) and intercellular action potential propagation (e.g., intercalated discs, gap junctions). Elegant genetic, biochemical, and imaging studies have revealed surprisingly dynamic regulation and turnover within such structures, rendering them subject to rapid alterations during stress and affecting their function. Population of cardiomyocyte subdomains with appropriate functional proteins is essential, with increasing studies finding that failure to deliver and/or maintain specific proteins within precise subcellular locations is a major cause of compromised cardiomyocyte function. Cellular regulatory hubs that have received substantial historical attention include altered gene expression at the transcriptional level and posttranslational modification of proteins. More recently, processes previously thought of as ‘constitutive’ such as post-transcriptional regulation at the point of protein translation and trafficking of de novo proteins within cardiomyocytes have been uncovered as highly dynamic and subject to pathological changes in diseased hearts. As our understanding grows, a clearer picture of the ‘healthy’ versus ‘diseased’ cardiomyocyte is emerging which, while complex, is unveiling new avenues for therapeutic intervention.

Dr. James Smyth
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 papers will be 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. Journal of Cardiovascular Development and Disease is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). 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

  • T-tubule
  • Sarcomere
  • Transcription
  • Translation
  • Trafficking
  • Cytoskeleton
  • Ion Channel
  • Intercalated Disc
  • Connexin
  • Stress

Published Papers (3 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Review

Review
Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine
J. Cardiovasc. Dev. Dis. 2021, 8(5), 52; https://doi.org/10.3390/jcdd8050052 - 05 May 2021
Cited by 2 | Viewed by 977
Abstract
Connexin (Cx43)-formed channels have been linked to cardiac arrhythmias and diseases of the heart associated with myocardial tissue loss and fibrosis. These pathologies include ischemic heart disease, ischemia-reperfusion injury, heart failure, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and Duchenne muscular dystrophy. A number [...] Read more.
Connexin (Cx43)-formed channels have been linked to cardiac arrhythmias and diseases of the heart associated with myocardial tissue loss and fibrosis. These pathologies include ischemic heart disease, ischemia-reperfusion injury, heart failure, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and Duchenne muscular dystrophy. A number of Cx43 mimetic peptides have been reported as therapeutic candidates for targeting disease processes linked to Cx43, including some that have advanced to clinical testing in humans. These peptides include Cx43 sequences based on the extracellular loop domains (e.g., Gap26, Gap 27, and Peptide5), cytoplasmic-loop domain (Gap19 and L2), and cytoplasmic carboxyl-terminal domain (e.g., JM2, Cx43tat, CycliCX, and the alphaCT family of peptides) of this transmembrane protein. Additionally, RYYN peptides binding to the Cx43 carboxyl-terminus have been described. In this review, we survey preclinical and clinical data available on short mimetic peptides based on, or directly targeting, Cx43, with focus on their potential for treating heart disease. We also discuss problems that have caused reluctance within the pharmaceutical industry to translate peptidic therapeutics to the clinic, even when supporting preclinical data is strong. These issues include those associated with the administration, stability in vivo, and tissue penetration of peptide-based therapeutics. Finally, we discuss novel drug delivery technologies including nanoparticles, exosomes, and other nanovesicular carriers that could transform the clinical and commercial viability of Cx43-targeting peptides in treatment of heart disease, stroke, cancer, and other indications requiring oral or parenteral administration. Some of these newly emerging approaches to drug delivery may provide a path to overcoming pitfalls associated with the drugging of peptide therapeutics. Full article
(This article belongs to the Special Issue Cardiomyopathy at the Sub-Cellular Level)
Show Figures

Figure 1

Review
Arrhythmogenic Cardiomyopathy: Molecular Insights for Improved Therapeutic Design
J. Cardiovasc. Dev. Dis. 2020, 7(2), 21; https://doi.org/10.3390/jcdd7020021 - 26 May 2020
Cited by 4 | Viewed by 1463
Abstract
Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, [...] Read more.
Arrhythmogenic cardiomyopathy (ACM) is an inherited disorder characterized by structural and electrical cardiac abnormalities, including myocardial fibro-fatty replacement. Its pathological ventricular substrate predisposes subjects to an increased risk of sudden cardiac death (SCD). ACM is a notorious cause of SCD in young athletes, and exercise has been documented to accelerate its progression. Although the genetic culprits are not exclusively limited to the intercalated disc, the majority of ACM-linked variants reside within desmosomal genes and are transmitted via Mendelian inheritance patterns; however, penetrance is highly variable. Its natural history features an initial “concealed phase” that results in patients being vulnerable to malignant arrhythmias prior to the onset of structural changes. Lack of effective therapies that target its pathophysiology renders management of patients challenging due to its progressive nature, and has highlighted a critical need to improve our understanding of its underlying mechanistic basis. In vitro and in vivo studies have begun to unravel the molecular consequences associated with disease causing variants, including altered Wnt/β-catenin signaling. Characterization of ACM mouse models has facilitated the evaluation of new therapeutic approaches. Improved molecular insight into the condition promises to usher in novel forms of therapy that will lead to improved care at the clinical bedside. Full article
(This article belongs to the Special Issue Cardiomyopathy at the Sub-Cellular Level)
Show Figures

Figure 1

Review
Translating Translation to Mechanisms of Cardiac Hypertrophy
J. Cardiovasc. Dev. Dis. 2020, 7(1), 9; https://doi.org/10.3390/jcdd7010009 - 10 Mar 2020
Cited by 7 | Viewed by 1549
Abstract
Cardiac hypertrophy in response to chronic pathological stress is a common feature occurring with many forms of heart disease. This pathological hypertrophic growth increases the risk for arrhythmias and subsequent heart failure. While several factors promoting cardiac hypertrophy are known, the molecular mechanisms [...] Read more.
Cardiac hypertrophy in response to chronic pathological stress is a common feature occurring with many forms of heart disease. This pathological hypertrophic growth increases the risk for arrhythmias and subsequent heart failure. While several factors promoting cardiac hypertrophy are known, the molecular mechanisms governing the progression to heart failure are incompletely understood. Recent studies on altered translational regulation during pathological cardiac hypertrophy are contributing to our understanding of disease progression. In this brief review, we describe how the translational machinery is modulated for enhanced global and transcript selective protein synthesis, and how alternative modes of translation contribute to the disease state. Attempts at controlling translational output through targeting of mTOR and its regulatory components are detailed, as well as recently emerging targets for pre-clinical investigation. Full article
(This article belongs to the Special Issue Cardiomyopathy at the Sub-Cellular Level)
Show Figures

Figure 1

Back to TopTop