10th Anniversary of JCDD—'Cardiac Development and Regeneration' Section — from Development to Regeneration

A special issue of Journal of Cardiovascular Development and Disease (ISSN 2308-3425). This special issue belongs to the section "Cardiac Development and Regeneration".

Deadline for manuscript submissions: 15 December 2024 | Viewed by 10258

Special Issue Editors


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Guest Editor
Department Nephropathology, Institute of Patholology, Friedrich-Alexander-Universität Erlangen-Nürnberg, D-97054 Erlangen, Germany
Interests: heart; skeletal muscle; 3D bioprinting; electroconductive materials; cancer biology; kidney
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Guest Editor
Department of Biochemistry & Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA
Interests: zebrafish heart regeneration; coronary vessel development and re-vascularization; cardiac lymphatic vessel development; lymphangiogenesis

Special Issue Information

Dear Colleagues,

We are celebrating the 10th anniversary of the section “Cardiac Development and Regeneration” of the Journal of Cardiovascular Development and Disease with a Special Issue focusing on the advances in cardiac regeneration, including relevant discoveries in heart development during the last 10 years. 

We would like to take this opportunity to thank our readers, authors, peer reviewers, editors, journal staff, and all other people that have contributed to the success of the Journal of Cardiovascular Development and Disease.

In the last 10 years, major advances have been made in understanding heart development and in identifying potential therapeutic strategies to treat heart diseases. Examples include the identification of pdgfrb+ cells regulating coronary vessel development and revascularization during heart regeneration, the establishment of cardiac organoids, 3D bioprinting of a four-chambered heart, understanding the nuclear MTOC in cardiomyocytes, modRNA-based heart therapies, and utilizing the Hippo pathway for heart regeneration based on cardiomyocyte proliferation. The purpose of this Special Issue is to review and comment on these and similar advances and to present novel related findings.

It is a real pleasure to serve as guest editors of this Special Issue. We invite you to contribute original research manuscripts, short communications, up-to-date review articles, and commentaries on a trendy or hot topic for peer-review and possible publication.

Prof. Dr. Felix B. Engel
Dr. Ching-Ling (Ellen) Lien
Guest Editors

Manuscript Submission Information

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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 2700 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

  • cardiomyocyte proliferation
  • cardiac tissue engineering
  • 3D bioprinting
  • vascular regeneration
  • vascular tissue engineering
  • 3D bioprinting
  • cardiac organoids
  • hiPSC-differentiation
  • injectable materials

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Published Papers (6 papers)

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Research

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26 pages, 14150 KiB  
Article
New Insights on the Formation of the Mitral Valve Chordae Tendineae in Fetal Life
by Meghan Martin, Kate Gillett, Parker Whittick and Sarah Melissa Wells
J. Cardiovasc. Dev. Dis. 2024, 11(11), 367; https://doi.org/10.3390/jcdd11110367 - 15 Nov 2024
Viewed by 341
Abstract
There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model; in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during [...] Read more.
There is an increasing understanding that some mitral valve pathologies have developmental origins. The time course of valvulogenesis varies by animal model; in cattle, the branched chordae tendineae architecture becomes fully developed at full term. The mechanism by which chordae tendineae bifurcate during fetal development remains unknown. The current study presents a detailed description of bovine chordae tendineae formation and bifurcation during fetal development. Analysis of Movat Pentachrome-stained histological sections of the developing mitral valve apparatus was accompanied by micro-CT imaging. TEM imaging of chordae branches and common trunks allowed the measurement of collagen fibril diameter distributions. We observed a proteoglycan-rich “transition zone” at the junction between the fetal mitral valve anterior leaflet and chordae tendineae with “perforations” lined by MMP1/2 and Ki-67 expressing endothelial cells. This region also contained clusters of proliferating endothelial cells within the bulk of the tissue. We hypothesize this zone marks a region where chordae tendineae bifurcate during fetal development. In particular, perforations created by localized MMP activity serve as a site for the initiation of a “split” of a single chordae attachment into two. This is supported by TEM results that suggest a similar population of collagen fibrils runs from the branches into a common trunk. A clear understanding of normal mitral valvulogenesis and its signaling mechanisms will be crucial in developing therapeutics and/or tissue-engineered valve replacements. Full article
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19 pages, 7552 KiB  
Article
Differential Development of the Chordae Tendineae and Anterior Leaflet of the Bovine Mitral Valve
by Meghan Martin, Chih-Ying Chen, Timothy McCowan and Sarah Wells
J. Cardiovasc. Dev. Dis. 2024, 11(4), 106; https://doi.org/10.3390/jcdd11040106 - 29 Mar 2024
Viewed by 1870
Abstract
There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish, chicks, and small mammalian models, longitudinal studies in large [...] Read more.
There is increasing evidence that some adult mitral valve pathologies may have developmental origins involving errors in cell signaling and protein deposition during valvulogenesis. While early and late gestational stages are well-documented in zebrafish, chicks, and small mammalian models, longitudinal studies in large mammals with a similar gestational period to humans are lacking. Further, the mechanism of chordae tendineae formation and multiplication remains unclear. The current study presents a comprehensive examination of mitral anterior leaflet and chordae tendineae development in a bovine model (a large mammal with the same gestational period as humans). Remarkably distinct from small mammals, bovine development displayed early branched chordae, with increasing attachments only until birth, while the anterior leaflet grew both during gestation and postnatally. Chordae also exhibited accelerated collagen deposition, maturation, and crimp development during gestation. These findings suggest that the bovine anterior leaflet and chordae tendineae possess unique processes of development despite being a continuous collagenous structure and could provide greater insight into human valve development. Full article
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Review

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21 pages, 808 KiB  
Review
Direct Cardiac Reprogramming in the Age of Computational Biology
by Rachelle Ambroise, Paige Takasugi, Jiandong Liu and Li Qian
J. Cardiovasc. Dev. Dis. 2024, 11(9), 273; https://doi.org/10.3390/jcdd11090273 - 4 Sep 2024
Viewed by 954
Abstract
Heart disease continues to be one of the most fatal conditions worldwide. This is in part due to the maladaptive remodeling process by which ischemic cardiac tissue is replaced with a fibrotic scar. Direct cardiac reprogramming presents a unique solution for restoring injured [...] Read more.
Heart disease continues to be one of the most fatal conditions worldwide. This is in part due to the maladaptive remodeling process by which ischemic cardiac tissue is replaced with a fibrotic scar. Direct cardiac reprogramming presents a unique solution for restoring injured cardiac tissue through the direct conversion of fibroblasts into induced cardiomyocytes, bypassing the transition through a pluripotent state. Since its inception in 2010, direct cardiac reprogramming using the transcription factors Gata4, Mef2c, and Tbx5 has revolutionized the field of cardiac regenerative medicine. Just over a decade later, the field has rapidly evolved through the expansion of identified molecular and genetic factors that can be used to optimize reprogramming efficiency. The integration of computational tools into the study of direct cardiac reprogramming has been critical to this progress. Advancements in transcriptomics, epigenetics, proteomics, genome editing, and machine learning have not only enhanced our understanding of the underlying mechanisms driving this cell fate transition, but have also driven innovations that push direct cardiac reprogramming closer to clinical application. This review article explores how these computational advancements have impacted and continue to shape the field of direct cardiac reprogramming. Full article
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16 pages, 2737 KiB  
Review
Developmental Changes in the Excitation–Contraction Mechanisms of the Ventricular Myocardium and Their Sympathetic Regulation in Small Experimental Animals
by Shogo Hamaguchi, Naoki Agata, Maika Seki, Iyuki Namekata and Hikaru Tanaka
J. Cardiovasc. Dev. Dis. 2024, 11(9), 267; https://doi.org/10.3390/jcdd11090267 - 29 Aug 2024
Viewed by 1108
Abstract
The developmental changes in the excitation–contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in [...] Read more.
The developmental changes in the excitation–contraction mechanisms of the ventricular myocardium of small animals (guinea pig, rat, mouse) and their sympathetic regulation will be summarized. The action potential duration monotonically decreases during pre- and postnatal development in the rat and mouse, while in the guinea pig it decreases during the fetal stage but turns into an increase just before birth. Such changes can be attributed to changes in the repolarizing potassium currents. The T-tubule and the sarcoplasmic reticulum are scarcely present in the fetal cardiomyocyte, but increase during postnatal development. This causes a developmental shift in the Ca2+ handling from a sarcolemma-dependent mechanism to a sarcoplasmic reticulum-dependent mechanism. The sensitivity for beta-adrenoceptor-mediated positive inotropy decreases during early postnatal development, which parallels the increase in sympathetic nerve innervation. The alpha-adrenoceptor-mediated inotropy in the mouse changes from positive in the neonate to negative in the adult. This can be explained by the change in the excitation–contraction mechanism mentioned above. The shortening of the action potential duration enhances trans-sarcolemmal Ca2+ extrusion by the Na+-Ca2+ exchanger. The sarcoplasmic reticulum-dependent mechanism of contraction in the adult allows Na+-Ca2+ exchanger activity to cause negative inotropy, a mechanism not observed in neonatal myocardium. Such developmental studies would provide clues towards a more comprehensive understanding of cardiac function. Full article
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27 pages, 4960 KiB  
Review
The Functional Significance of Cardiac Looping: Comparative Embryology, Anatomy, and Physiology of the Looped Design of Vertebrate Hearts
by Jörg Männer
J. Cardiovasc. Dev. Dis. 2024, 11(8), 252; https://doi.org/10.3390/jcdd11080252 - 17 Aug 2024
Viewed by 1520
Abstract
The flow path of vertebrate hearts has a looped configuration characterized by curved (sigmoid) and twisted (chiral) components. The looped heart design is phylogenetically conserved among vertebrates and is thought to represent a significant determinant of cardiac pumping function. It evolves during the [...] Read more.
The flow path of vertebrate hearts has a looped configuration characterized by curved (sigmoid) and twisted (chiral) components. The looped heart design is phylogenetically conserved among vertebrates and is thought to represent a significant determinant of cardiac pumping function. It evolves during the embryonic period of development by a process called “cardiac looping”. During the past decades, remarkable progress has been made in the uncovering of genetic, molecular, and biophysical factors contributing to cardiac looping. Our present knowledge of the functional consequences of cardiac looping lags behind this impressive progress. This article provides an overview and discussion of the currently available information on looped heart design and its implications for the pumping function. It is emphasized that: (1) looping seems to improve the pumping efficiency of the valveless embryonic heart. (2) bilaterally asymmetric (chiral) looping plays a central role in determining the alignment and separation of the pulmonary and systemic flow paths in the multi-chambered heart of tetrapods. (3) chiral looping is not needed for efficient pumping of the two-chambered hearts of fish. (4) it is the sigmoid curving of the flow path that may improve the pumping efficiency of lower as well as higher vertebrate hearts. Full article
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14 pages, 953 KiB  
Review
Cell-Specific mRNA Therapeutics for Cardiovascular Diseases and Regeneration
by Raj Kishore and Ajit Magadum
J. Cardiovasc. Dev. Dis. 2024, 11(2), 38; https://doi.org/10.3390/jcdd11020038 - 26 Jan 2024
Cited by 1 | Viewed by 3656
Abstract
Cardiovascular diseases (CVDs) represent a significant global health burden, demanding innovative therapeutic approaches. In recent years, mRNA therapeutics have emerged as a promising strategy to combat CVDs effectively. Unlike conventional small-molecule drugs, mRNA therapeutics enable the direct modulation of cellular functions by delivering [...] Read more.
Cardiovascular diseases (CVDs) represent a significant global health burden, demanding innovative therapeutic approaches. In recent years, mRNA therapeutics have emerged as a promising strategy to combat CVDs effectively. Unlike conventional small-molecule drugs, mRNA therapeutics enable the direct modulation of cellular functions by delivering specific mRNA molecules to target cells. This approach offers unprecedented advantages, including the ability to harness endogenous cellular machinery for protein synthesis, thus allowing precise control over gene expression without insertion into the genome. This review summarizes the current status of the potential of cell-specific mRNA therapeutics in the context of cardiovascular diseases. First, it outlines the challenges associated with traditional CVD treatments and emphasizes the need for targeted therapies. Subsequently, it elucidates the underlying principles of mRNA therapeutics and the development of advanced delivery systems to ensure cell-specificity and enhanced efficacy. Notably, innovative delivery methods such as lipid nanoparticles and exosomes have shown promise in improving the targeted delivery of mRNA to cardiac cells, activated fibroblasts, and other relevant cell types. Furthermore, the review highlights the diverse applications of cell-specific mRNA therapeutics in addressing various aspects of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure, and arrhythmias. By modulating key regulatory genes involved in cardiomyocyte proliferation, inflammation, angiogenesis, tissue repair, and cell survival, mRNA therapeutics hold the potential to intervene at multiple stages of CVD pathogenesis. Despite its immense potential, this abstract acknowledges the challenges in translating cell-specific mRNA therapeutics from preclinical studies to clinical applications like off-target effects and delivery. In conclusion, cell-specific mRNA therapeutics have emerged as a revolutionary gene therapy approach for CVD, offering targeted interventions with the potential to significantly improve patient outcomes. Full article
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