Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure

E.D. van Deel; M. Snelders; N. van Vliet; L. Te Riet; T.P.P. van den Bosch; L.R. Fiedler; A.C.C. van Spreeuwel; N.A.M. Bax; N. Boontje; C.M. Halabi; T. Sasaki; D.P. Reinhardt; J. van der Velden; C.V.C. Bouten; J.H. von der Thüsen; A.H.J. Danser; D.J. Duncker; M.D. Schneider; I. van der Pluijm; J. Essers

doi:10.1038/s42003-025-08087-8

Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure

E.D. van Deel
, M. Snelders
, N. van Vliet
, L. Te Riet
, T.P.P. van den Bosch
, L.R. Fiedler
, A.C.C. van Spreeuwel
, N.A.M. Bax
, N. Boontje
, C.M. Halabi
, T. Sasaki
, D.P. Reinhardt
, J. van der Velden
, C.V.C. Bouten
, J.H. von der Thüsen
, A.H.J. Danser
, D.J. Duncker
, M.D. Schneider
, I. van der Pluijm
, J. Essers (Corresponding author-nrf)

Onderzoeksoutput: Bijdrage aan tijdschrift › Tijdschriftartikel › Academic › peer review

1 Citaat (Scopus)

29 Downloads (Pure)

Samenvatting

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.

Originele taal-2	Engels
Artikelnummer	661
Aantal pagina's	16
Tijdschrift	Communications biology
Volume	8
Nummer van het tijdschrift	1
DOI's	https://doi.org/10.1038/s42003-025-08087-8
Status	Gepubliceerd - 24 apr. 2025

Bibliografische nota

Financiering

The authors would like to thank Ingrid van den Berg\u2013Garrelds for her measurements of the plasma renin concentrations in fibulin-4 and fibulin-4 mice. This work was supported by the \u201CUNESCO-L\u2019Or\u00E9al for Woman in Science Fellowship\u201D (E.D.D.), the Netherlands Institute for Regenerative medicine (FES0908, A.C.C.S., N.A.M.B and C.V.C.B.), Genetic Aortic Disorders Association Canada and Natural Sciences and Engineering Research Council of Canada (D.P.R.), the British Heart Foundation Centre of Research Excellence and British Heart Foundation Simon Marks Chair in Regenerative Cardiology (M.D.S.), the \u201CLijf en Leven\u201D-grant (2008): \u201CEarly detection and diagnosis of aneurysms and heart valve abnormalities\u201D (J.E.) and Dilating versus Stenosing arterial disease (2011) (E.D.D., I.P., and J.E.), the HeartCHIP II Health~Holland project (grant number EMCLSH19005, M.S.), the Dutch CardioVascular Alliance, an initiative with financial support of the Dutch Heart Foundation (2017B018-ARENA-PRIME & 2021B008-RECONNEXT, D.J.D.), and TKI-LSH grant Quantitative in vivo imaging of heart failure (HF-Image, LSHM18002, N.V.).

Toegang tot document

10.1038/s42003-025-08087-8

pdfDefinitieve gepubliceerde versie, 6,21 MB

Andere bestanden en links

Link naar publicatie in Scopus

Citeer dit

van Deel, E. D., Snelders, M., van Vliet, N., Te Riet, L., van den Bosch, T. P. P., Fiedler, L. R., van Spreeuwel, A. C. C., Bax, N. A. M., Boontje, N., Halabi, C. M., Sasaki, T., Reinhardt, D. P., van der Velden, J., Bouten, C. V. C., von der Thüsen, J. H., Danser, A. H. J., Duncker, D. J., Schneider, M. D., van der Pluijm, I., & Essers, J. (2025). Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure. Communications biology, 8(1), Artikel 661. https://doi.org/10.1038/s42003-025-08087-8

@article{23a122a018b442c7b9808603279368a3,

title = "Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure",

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. ",

keywords = "Animals, Cardiomegaly/metabolism, Mice, Heart Failure/metabolism, Extracellular Matrix Proteins/metabolism, Mice, Inbred C57BL, Myocardium/metabolism, Male, Myocytes, Cardiac/metabolism",

author = "\{van Deel\}, E.D. and M. Snelders and \{van Vliet\}, N. and \{Te Riet\}, L. and \{van den Bosch\}, T.P.P. and L.R. Fiedler and \{van Spreeuwel\}, A.C.C. and N.A.M. Bax and N. Boontje and C.M. Halabi and T. Sasaki and D.P. Reinhardt and \{van der Velden\}, J. and C.V.C. Bouten and \{von der Th{\"u}sen\}, J.H. and A.H.J. Danser and D.J. Duncker and M.D. Schneider and \{van der Pluijm\}, I. and J. Essers",

note = "{\textcopyright} 2025. The Author(s).",

year = "2025",

month = apr,

day = "24",

doi = "10.1038/s42003-025-08087-8",

language = "English",

volume = "8",

journal = "Communications biology",

issn = "2399-3642",

publisher = "Springer Nature",

number = "1",

}

van Deel, ED, Snelders, M, van Vliet, N, Te Riet, L, van den Bosch, TPP, Fiedler, LR, van Spreeuwel, ACC, Bax, NAM, Boontje, N, Halabi, CM, Sasaki, T, Reinhardt, DP, van der Velden, J, Bouten, CVC, von der Thüsen, JH, Danser, AHJ, Duncker, DJ, Schneider, MD, van der Pluijm, I & Essers, J 2025, 'Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure', Communications biology, vol. 8, nr. 1, 661. https://doi.org/10.1038/s42003-025-08087-8

TY - JOUR

T1 - Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure

AU - van Deel, E.D.

AU - Snelders, M.

AU - van Vliet, N.

AU - Te Riet, L.

AU - van den Bosch, T.P.P.

AU - Fiedler, L.R.

AU - van Spreeuwel, A.C.C.

AU - Bax, N.A.M.

AU - Boontje, N.

AU - Halabi, C.M.

AU - Sasaki, T.

AU - Reinhardt, D.P.

AU - van der Velden, J.

AU - Bouten, C.V.C.

AU - von der Thüsen, J.H.

AU - Danser, A.H.J.

AU - Duncker, D.J.

AU - Schneider, M.D.

AU - van der Pluijm, I.

A2 - Essers, J.

PY - 2025/4/24

Y1 - 2025/4/24

N2 - 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.

AB - 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.

KW - Animals

KW - Cardiomegaly/metabolism

KW - Mice

KW - Heart Failure/metabolism

KW - Extracellular Matrix Proteins/metabolism

KW - Mice, Inbred C57BL

KW - Myocardium/metabolism

KW - Male

KW - Myocytes, Cardiac/metabolism

UR - https://www.scopus.com/pages/publications/105003464461

U2 - 10.1038/s42003-025-08087-8

DO - 10.1038/s42003-025-08087-8

M3 - Article

C2 - 40274989

SN - 2399-3642

VL - 8

JO - Communications biology

JF - Communications biology

IS - 1

M1 - 661

ER -

Induction of cardiac fibulin-4 protects against pressure overload-induced cardiac hypertrophy and heart failure

Samenvatting

Bibliografische nota

Financiering

Toegang tot document

Andere bestanden en links

Vingerafdruk

Citeer dit