Submit to Special Issue Submit Abstract to Special Issue Review for Cells Propose a Special Issue

Journal Browser

► Journal Browser

Cardiac Fibrosis: From Pathogenesis to Targeted Therapies

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 4121

Share This Special Issue

Special Issue Editors

Dr. Zhaokang Cheng

E-Mail Website
Guest Editor

College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, WA, USA
Interests: heart disease; cell death; hypertrophy; fibrosis

Dr. Xing Fu

E-Mail Website
Guest Editor

School of Animal Sciences, Louisiana State University, Baton Rouge, LA, USA
Interests: fibroblast; fibrosis; epigenetics; heart disease; stem cell

Special Issue Information

Dear Colleagues,

Despite the recent advances in diagnosis and therapies, cardiovascular diseases remain the leading cause of death worldwide. Many types of cardiovascular diseases are associated with cardiac fibrosis, which is characterized by an increase in the extracellular matrix in the heart. Extracellular matrix proteins are primarily produced by cardiac fibroblasts. In response to pathological injury, quiescent fibroblasts become active and differentiate into myofibroblasts, leading to the synthesis and secretion of extracellular matrix proteins. The secreted extracellular matrix proteins may help to maintain the structural integrity of the heart after injuries. However, prolonged fibrosis interferes with myocardial contraction and relaxation, resulting in reduced compliance, cardiac dysfunction, and eventually heart failure. At present, there is no FDA-approved drug that specifically targets cardiac fibrosis. Understanding the molecular and cellular mechanisms of cardiac fibrosis could reveal novel signaling pathways that can be therapeutically targeted for cardioprotection.

In this Special Issue “Cardiac Fibrosis: From Pathogenesis to Targeted Therapies”, we are interested in the following topics:

Novel mechanisms of heart diseases related to cardiac fibrosis, including myocardial infarction, ischemia/reperfusion injury, myocardial hypertrophy, myocarditis, cardiomyopathies and heart failure, etc.
In vitro and/or in vivo studies of cardiac fibroblast activation and differentiation, as well as extracellular matrix protein production, secretion, and degradation.
Novel therapeutics and techniques for the prevention and treatment of cardiac fibrosis.
Novel biomarkers/imaging techniques for the detection and diagnosis of cardiac fibrosis.

Dr. Zhaokang Cheng
Dr. Xing Fu
Guest Editors

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. Cells is an international peer-reviewed open access semimonthly 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

heart failure
cardiac fibroblasts
cardiac myocytes
fibrosis
remodeling

Published Papers (3 papers)

Download All Papers

Research

Jump to: Review

22 pages, 8130 KiB

Open AccessArticle

Cardiomyocyte-Specific Loss of Glutamyl-prolyl-tRNA Synthetase Leads to Disturbed Protein Homeostasis and Dilated Cardiomyopathy

by Jiangbin Wu, Jared Hollinger, Emily Bonanno, Feng Jiang and Peng Yao

Cells 2024, 13(1), 35; https://doi.org/10.3390/cells13010035 - 22 Dec 2023

Cited by 1 | Viewed by 1145

Abstract

Glutamyl-prolyl-tRNA synthetase (EPRS1), an aminoacyl-tRNA synthetase (ARS) ligating glutamic acid and proline to their corresponding tRNAs, plays an essential role in decoding proline codons during translation elongation. The physiological function of EPRS1 in cardiomyocytes (CMs) and the potential effects of the CM-specific loss of Eprs1 remain unknown. Here, we found that heterozygous Eprs1 knockout in CMs does not cause any significant changes in CM hypertrophy induced by pressure overload, while homozygous knockout leads to dilated cardiomyopathy, heart failure, and lethality at around 1 month after Eprs1 deletion. The transcriptomic profiling of early-stage Eprs1 knockout hearts suggests a significantly decreased expression of multiple ion channel genes and an increased gene expression in proapoptotic pathways and integrated stress response. Proteomic analysis shows decreased protein expression in multi-aminoacyl-tRNA synthetase complex components, fatty acids, and branched-chain amino acid metabolic enzymes, as well as a compensatory increase in cytosolic translation machine-related proteins. Immunoblot analysis indicates that multiple proline-rich proteins were reduced at the early stage, which might contribute to the cardiac dysfunction of Eprs1 knockout mice. Taken together, this study demonstrates the physiological and molecular outcomes of loss-of-function of Eprs1 in vivo and provides valuable insights into the potential side effects on CMs, resulting from the EPRS1-targeting therapeutic approach. Full article

(This article belongs to the Special Issue Cardiac Fibrosis: From Pathogenesis to Targeted Therapies)

► Show Figures

Figure 1

16 pages, 2681 KiB

Open AccessArticle

Col1a2-Deleted Mice Have Defective Type I Collagen and Secondary Reactive Cardiac Fibrosis with Altered Hypertrophic Dynamics

by Stephanie L. K. Bowers, Qinghang Meng, Yasuhide Kuwabara, Jiuzhou Huo, Rachel Minerath, Allen J. York, Michelle A. Sargent, Vikram Prasad, Anthony J. Saviola, David Ceja Galindo, Kirk C. Hansen, Ronald J. Vagnozzi, Katherine E. Yutzey and Jeffery D. Molkentin

Cells 2023, 12(17), 2174; https://doi.org/10.3390/cells12172174 - 30 Aug 2023

Cited by 5 | Viewed by 1832

Abstract

Rationale: The adult cardiac extracellular matrix (ECM) is largely comprised of type I collagen. In addition to serving as the primary structural support component of the cardiac ECM, type I collagen also provides an organizational platform for other ECM proteins, matricellular proteins, and signaling components that impact cellular stress sensing in vivo. Objective: Here we investigated how the content and integrity of type I collagen affect cardiac structure function and response to injury. Methods and Results: We generated and characterized Col1a2^−/− mice using standard gene targeting. Col1a2^−/− mice were viable, although by young adulthood their hearts showed alterations in ECM mechanical properties, as well as an unanticipated activation of cardiac fibroblasts and induction of a progressive fibrotic response. This included augmented TGFβ activity, increases in fibroblast number, and progressive cardiac hypertrophy, with reduced functional performance by 9 months of age. Col1a2-loxP-targeted mice were also generated and crossed with the tamoxifen-inducible Postn-MerCreMer mice to delete the Col1a2 gene in myofibroblasts with pressure overload injury. Interestingly, while germline Col1a2^−/− mice showed gradual pathologic hypertrophy and fibrosis with aging, the acute deletion of Col1a2 from activated adult myofibroblasts showed a loss of total collagen deposition with acute cardiac injury and an acute reduction in pressure overload-induce cardiac hypertrophy. However, this reduction in hypertrophy due to myofibroblast-specific Col1a2 deletion was lost after 2 and 6 weeks of pressure overload, as fibrotic deposition accumulated. Conclusions: Defective type I collagen in the heart alters the structural integrity of the ECM and leads to cardiomyopathy in adulthood, with fibroblast expansion, activation, and alternate fibrotic ECM deposition. However, acute inhibition of type I collagen production can have an anti-fibrotic and anti-hypertrophic effect. Full article

(This article belongs to the Special Issue Cardiac Fibrosis: From Pathogenesis to Targeted Therapies)

► Show Figures

Graphical abstract

Review

Jump to: Research

19 pages, 1506 KiB

Open AccessReview

Targeting Interactions between Fibroblasts and Macrophages to Treat Cardiac Fibrosis

by Bo Yang, Yan Qiao, Dong Yan and Qinghang Meng

Cells 2024, 13(9), 764; https://doi.org/10.3390/cells13090764 - 30 Apr 2024

Viewed by 675

Abstract

Excessive extracellular matrix (ECM) deposition is a defining feature of cardiac fibrosis. Most notably, it is characterized by a significant change in the concentration and volume fraction of collagen I, a disproportionate deposition of collagen subtypes, and a disturbed ECM network arrangement, which directly affect the systolic and diastolic functions of the heart. Immune cells that reside within or infiltrate the myocardium, including macrophages, play important roles in fibroblast activation and consequent ECM remodeling. Through both direct and indirect connections to fibroblasts, monocyte-derived macrophages and resident cardiac macrophages play complex, bidirectional, regulatory roles in cardiac fibrosis. In this review, we discuss emerging interactions between fibroblasts and macrophages in physiology and pathologic conditions, providing insights for future research aimed at targeting macrophages to combat cardiac fibrosis. Full article

(This article belongs to the Special Issue Cardiac Fibrosis: From Pathogenesis to Targeted Therapies)

► Show Figures