Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome

Geva, Tal; Sanders, Stephen P.; Diógenes, Maria Suely Bezerra; Rockenmacher, Sol; Praagh, Richard Van

doi:10.1016/0002-9149(90)90979-b

Cited by 84 publications

(71 citation statements)

References 39 publications

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“…In keeping with a critical contribution of hemodynamic stress, heart failure and infantile death in children with the most severe presentation of MFS uniformly associate with significant volume overload (44,45) and can be delayed or even prevented by aggressive surgical intervention for valve dysfunction (46)(47)(48). In this study, we utilized a standardized PO (via TAC) as a conditional provocation in young mice heterozygous for a typical MFS-associated missense mutation in fibrillin-1.…”

Section: Discussionmentioning

confidence: 99%

Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

Rouf¹,

MacFarlane²,

Takimoto³

et al. 2017

JCI Insight

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Section: Discussionmentioning

confidence: 99%

Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

Rouf¹,

MacFarlane²,

Takimoto³

et al. 2017

JCI Insight

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“…Cardiac dysfunction is a common finding in severely affected MFS infants that is often accompanied by congestive heart failure (12,30,32). Subclinical cardiomyopathy is also a risk factor for adolescent and adult MFS patients, as surgical TAA repair can lead to an acute rise in LV afterload due to the low compliance of Dacron implants (12,31).…”

Section: Discussionmentioning

confidence: 99%

“…This experimental evidence has resulted in several clinical trials assessing the efficacy of losartan therapy against TAA progression in MFS patients (25)(26)(27)(28)(29). In contrast to the wealth of new information about TAA pathogenesis, heart dysfunction has not been characterized in Fbn1 mutant mice, with negative implications for improving the management of cardiac complications in MFS patients, particularly in severely affected children or following prophylactic TAA repair (6,(30)(31)(32).…”

Section: Introductionmentioning

confidence: 99%

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

Cook¹,

Carta²,

Bénard³

et al. 2014

J. Clin. Invest.

121

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Patients with Marfan syndrome (MFS), a multisystem disorder caused by mutations in the gene encoding the extracellular matrix (ECM) protein fibrillin 1, are unusually vulnerable to stress-induced cardiac dysfunction. The prevailing view is that MFS-associated cardiac dysfunction is the result of aortic and/or valvular disease. Here, we determined that dilated cardiomyopathy (DCM) in fibrillin 1-deficient mice is a primary manifestation resulting from ECM-induced abnormal mechanosignaling by cardiomyocytes. MFS mice displayed spontaneous emergence of an enlarged and dysfunctional heart, altered physical properties of myocardial tissue, and biochemical evidence of chronic mechanical stress, including increased angiotensin II type I receptor (AT1R) signaling and abated focal adhesion kinase (FAK) activity. Partial fibrillin 1 gene inactivation in cardiomyocytes was sufficient to precipitate DCM in otherwise phenotypically normal mice. Consistent with abnormal mechanosignaling, normal cardiac size and function were restored in MFS mice treated with an AT1R antagonist and in MFS mice lacking AT1R or β-arrestin 2, but not in MFS mice treated with an angiotensin-converting enzyme inhibitor or lacking angiotensinogen. Conversely, DCM associated with abnormal AT1R and FAK signaling was the sole abnormality in mice that were haploinsufficient for both fibrillin 1 and β1 integrin. Collectively, these findings implicate fibrillin 1 in the physiological adaptation of cardiac muscle to elevated workload.

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“…Mortality is high within the first year of life because of cardiac failure secondary to severe mitral valve regurgitation. 75 Almost all cases of neonatal Marfan syndrome are sporadic and are associated with mutations clustering within exons 24 through 32 of FBN1.…”

Section: Neonatal Marfan Syndromementioning

confidence: 99%

Health Supervision for Children With Marfan Syndrome

Tinkle¹,

Saal²,

Saul³

et al. 2013

Pediatrics

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Two-dimensional and Doppler echocardiographic and pathologic characteristics of the infantile Marfan syndrome

Cited by 84 publications

References 39 publications

Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

Nonmyocyte ERK1/2 signaling contributes to load-induced cardiomyopathy in Marfan mice

Abnormal muscle mechanosignaling triggers cardiomyopathy in mice with Marfan syndrome

Health Supervision for Children With Marfan Syndrome

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