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Special Issue "Extracellular Matrix in Heart Disease"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: 31 July 2020.

Special Issue Editor

Dr. Muneyoshi Okada
E-Mail Website
Guest Editor
Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Higashi 23 bancho 35–1, Towada, Aomori 034–8628, Japan
Interests: cardiovascular pharmacology; cardiovascular disease; myocardial infarction; cardiac hypertrophy; arrhythmia; heart failure; pulmonary arterial hypertension; fibrosis; extracellular matrix; cardiac fibroblast; cardiomyocyte; matricryptin/matrikine; matricellular protein; matrix metalloproteinase; cardiac electrophysiology

Special Issue Information

Dear Colleagues,

Components of the extracellular matrix (ECM), such as collagen, fibronectin, laminin, and proteoglycan, maintain cardiac structure and function by forming a complicated three-dimensional network. Cell–ECM interaction is also important for regulating the functions of cardiomyocytes and non-cardiomyocytes. An imbalance between the production and degradation of the ECM during the development and progression of heart disease is associated with pathological cardiac remodeling, including hypertrophy and fibrosis. Recently, it has been reported that matricellular proteins, a family of non-structural ECM proteins, and matricryptins/matrikines, bioactive fragments of ECM proteins, are involved in cardiac remodeling. In this Special Issue, we expect to gather novel knowledge that will lead to the discovery of drugs targeting the ECM and its fragments for heart disease.

Dr. Muneyoshi Okada
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. 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.


  • extracellular matrix
  • cardiac remodeling
  • fibrosis
  • hypertrophy
  • heart failure
  • fibroblast
  • cardiomyocyte
  • matricryptin/matrikine
  • matricellular protein
  • matrix metalloproteinase

Published Papers (1 paper)

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Open AccessArticle
TLR4 Stimulation Promotes Human AVIC Fibrogenic Activity through Upregulation of Neurotrophin 3 Production
Int. J. Mol. Sci. 2020, 21(4), 1276; https://doi.org/10.3390/ijms21041276 - 14 Feb 2020
Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease that manifests as progressive valvular fibrosis and calcification. An inflammatory milieu in valvular tissue promotes fibrosis and calcification. Aortic valve interstitial cell (AVIC) proliferation and the over-production of the extracellular matrix (ECM) [...] Read more.
Background: Calcific aortic valve disease (CAVD) is a chronic inflammatory disease that manifests as progressive valvular fibrosis and calcification. An inflammatory milieu in valvular tissue promotes fibrosis and calcification. Aortic valve interstitial cell (AVIC) proliferation and the over-production of the extracellular matrix (ECM) proteins contribute to valvular thickening. However, the mechanism underlying elevated AVIC fibrogenic activity remains unclear. Recently, we observed that AVICs from diseased aortic valves express higher levels of neurotrophin 3 (NT3) and that NT3 exerts pro-osteogenic and pro-fibrogenic effects on human AVICs. Hypothesis: Pro-inflammatory stimuli upregulate NT3 production in AVICs to promote fibrogenic activity in human aortic valves. Methods and Results: AVICs were isolated from normal human aortic valves and were treated with lipopolysaccharide (LPS, 0.20 µg/mL). LPS induced TLR4-dependent NT3 production. This effect of LPS was abolished by inhibition of the Akt and extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) pathways. The stimulation of TLR4 in human AVICs with LPS resulted in a greater proliferation rate and an upregulated production of matrix metallopeptidases-9 (MMP-9) and collagen III, as well as augmented collagen deposition. Recombinant NT3 promoted AVIC proliferation in a tropomyosin receptor kinase (Trk)-dependent fashion. The neutralization of NT3 or the inhibition of Trk suppressed LPS-induced AVIC fibrogenic activity. Conclusions: The stimulation of TLR4 in human AVICs upregulates NT3 expression and promotes cell proliferation and collagen deposition. The NT3-Trk cascade plays a critical role in the TLR4-mediated elevation of fibrogenic activity in human AVICs. Upregulated NT3 production by endogenous TLR4 activators may contribute to aortic valve fibrosis associated with CAVD progression. Full article
(This article belongs to the Special Issue Extracellular Matrix in Heart Disease)
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Review Article
Title: Role of extracellular matrix in the pathogenesis of patent ductus arteriosus
Authors: Jong Hau Hsu, etc.

Title: The diabetic, the hypertensive and the antracycline exposed heart: differences and similarities in extracellular remodeling
Authors: Kirsti Ytrehus, Anne D. Hafstad, etc.

Title: MMP and TIMP activity in extracellular matrix remodeling during left ventricular diastolic dysfunction: a systematic review
Authors: C.G.M. van Dijk and MM Krebber, C. Cheng, J.A. Joles, M.C. Verhaar

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