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<p>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<sup>+/+</sup>) C57Bl/6J;129 Sv mice subjected to transverse aortic constriction (TAC). In contrast, haploinsufficient fibulin-4<sup>+/R</sup> 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<sup>+/R</sup> 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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月24日

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  • 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

摘要

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.