Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
The prevailing view of fibulin-4 deficient mice is that the cardiac phenotype is the result of aortic and/or valvular disease. In the present study, we have tested whether the cardiac phenotype is, at least in part, the consequence of primary cardiac effects of fibulin-4. We have found fibulin-4 expression to be activated throughout the myocardium in wildtype (fibulin-4+/+) C57Bl/6J;129 Sv mice subjected to transverse aortic constriction (TAC). In contrast, haploinsufficient fibulin-4+/R mice exposed to severe TAC do not show this increase in myocardial fibulin-4 expression, but display altered physical properties of myocardial tissue. Moreover, TAC-induced cardiac fibrosis, pulmonary congestion, and mortality are aggravated in fibulin-4+/R mice. In vitro investigations of myocardial tissue show that fibulin-4 deficiency results in cardiomyocyte hypertrophy, and a decreased beating frequency and contractile force. In conclusion, we demonstrate functions for fibulin-4 in cardiac homeostasis and show that reduced fibulin-4 expression drives myocardial disease in response to cardiac pressure overload, independent of aortic valvular pathology.
Date Issued
2025-04-24
Date Acceptance
2025-04-14
Citation
Communications Biology, 2025, 8
ISSN
2399-3642
Publisher
Nature Portfolio
Journal / Book Title
Communications Biology
Volume
8
Copyright Statement
© The Author(s) 2025 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/40274989
PII: 10.1038/s42003-025-08087-8
Subjects
ANEURYSM
Biology
CARDIOMYOPATHY
CUTIS LAXA
DEFICIENT
ELASTOGENESIS
EXTRACELLULAR-MATRIX
GENE
GROWTH
LENGTH
Life Sciences & Biomedicine
Life Sciences & Biomedicine - Other Topics
MICE
Multidisciplinary Sciences
Science & Technology
Science & Technology - Other Topics
Publication Status
Published
Coverage Spatial
England
Article Number
661
Date Publish Online
2025-04-24