Intrinsic cardiomyopathy in Marfan syndrome: Results from in-vivo and ex-vivo studies of the Fbn1 C1039G/+ model and longitudinal findings in humans

Laurence Campens, Marjolijn Renard, Bram Trachet, Patrick Segers, Laura Muino Mosquera, Johan De Sutter, Lynn Sakai, Anne De Paepe, Julie De Backer

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Background:Mild intrinsic cardiomyopathy in patients with Marfan syndrome (MFS) has consistently been evidenced by independent research groups. So far, little is known about the long-term evolution and pathophysiology of this finding.Methods:To gain more insights into the pathophysiology of MFS-related cardiomyopathy, we performed in-vivo and ex-vivo studies of 11 Fbn1 C1039G/+ mice and 9 wild-type (WT) littermates. Serial ultrasound findings obtained in mice were correlated to the human phenotype. We therefore reassessed left ventricular (LV) function parameters over a 6-y follow-up period in 19 previously reported MFS patients, in whom we documented mild LV dysfunction.Results:Fbn1 C1039G/+ mice demonstrated LV contractile dysfunction. Subsequent ex-vivo studies of the myocardium of adult mutant mice revealed upregulation of TGFβ-related pathways and consistent abnormalities of the microfibrillar network, implicating a role for microfibrils in the mechanical properties of the myocardium. Echocardiographic parameters did not indicate clinical significant deterioration of LV function during follow-up in our patient cohort.Conclusion:In analogy with what is observed in the majority of MFS patients, the Fbn1 C1039G/+ mouse model demonstrates mild intrinsic LV dysfunction. Both extracellular matrix and molecular alterations are implicated in MFS-related cardiomyopathy. This model may now enable us to study therapeutic interventions on the myocardium in MFS.

Original languageEnglish (US)
Pages (from-to)256-263
Number of pages8
JournalPediatric Research
Volume78
Issue number3
DOIs
StatePublished - Sep 19 2015

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

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