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A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy.

Publication ,  Conference
Cavanaugh, NB; Qian, L; Westergaard, NM; Kutschke, WJ; Born, EJ; Turek, JW
Published in: Ann Thorac Surg
August 2017

BACKGROUND: Marfan syndrome (MFS) represents a genetic disorder with variable phenotypic expression. The main cardiovascular sequelae of MFS include aortic aneurysm/dissection and cardiomyopathy. Although significant advances in the understanding of transforming growth factor beta signaling have led to promising therapeutic targets for the treatment of aortopathy, clinical studies have tempered this optimism. In particular, these studies suggest additional signaling pathways that play a significant role in disease progression. To date, studies aimed at elucidating molecular mechanisms involved in MFS-induced disease progression have been hampered by the lack of an accelerated disease model. METHODS: Wild-type B6.129 mice and MFS Fbn1C1039G/+ mice underwent subcutaneous, cervical osmotic minipump installation with sodium chloride (wild-type mice, n = 39; MFS mice, n = 12) or angiotensin II, 4.5 mg/kg daily (wild-type mice, n = 11; MFS mice; n = 35) for as long as 28 days. Hemodynamic measurements were obtained throughout the experiment. Aortas and hearts were analyzed by transthoracic echocardiography and histopathology study. RESULTS: This accelerated murine MFS model replicates increased mortality from MFS-related maladies (20.0%, 39.3%, and 52.9% at 10, 14, and 28 days, respectively). Aortic diameters in accelerated MFS mice were significantly enlarged at 10 days after minipump implantation and correlated with a higher degree of elastin fragmentation. Accelerated MFS mice also demonstrated dilated cardiomyopathy at 14 days, even without aortic insufficiency, suggesting an intrinsic etiology. CONCLUSIONS: A novel in vivo model consisting of subcutaneously delivered angiotensin II in MFS mice reproducibly causes accelerated aortic aneurysm formation and cardiomyopathy. This model allows for better investigation of MFS sequelae by rapid experimental processes.

Duke Scholars

Published In

Ann Thorac Surg

DOI

EISSN

1552-6259

Publication Date

August 2017

Volume

104

Issue

2

Start / End Page

657 / 665

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Respiratory System
  • Mice, Mutant Strains
  • Mice
  • Marfan Syndrome
  • Heart Ventricles
  • Echocardiography
  • Disease Progression
  • Disease Models, Animal
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cavanaugh, N. B., Qian, L., Westergaard, N. M., Kutschke, W. J., Born, E. J., & Turek, J. W. (2017). A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy. In Ann Thorac Surg (Vol. 104, pp. 657–665). Netherlands. https://doi.org/10.1016/j.athoracsur.2016.10.077
Cavanaugh, Nicholas B., Lan Qian, Nicole M. Westergaard, William J. Kutschke, Ella J. Born, and Joseph W. Turek. “A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy.” In Ann Thorac Surg, 104:657–65, 2017. https://doi.org/10.1016/j.athoracsur.2016.10.077.
Cavanaugh NB, Qian L, Westergaard NM, Kutschke WJ, Born EJ, Turek JW. A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy. In: Ann Thorac Surg. 2017. p. 657–65.
Cavanaugh, Nicholas B., et al. “A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy.Ann Thorac Surg, vol. 104, no. 2, 2017, pp. 657–65. Pubmed, doi:10.1016/j.athoracsur.2016.10.077.
Cavanaugh NB, Qian L, Westergaard NM, Kutschke WJ, Born EJ, Turek JW. A Novel Murine Model of Marfan Syndrome Accelerates Aortopathy and Cardiomyopathy. Ann Thorac Surg. 2017. p. 657–665.
Journal cover image

Published In

Ann Thorac Surg

DOI

EISSN

1552-6259

Publication Date

August 2017

Volume

104

Issue

2

Start / End Page

657 / 665

Location

Netherlands

Related Subject Headings

  • Transforming Growth Factor beta
  • Signal Transduction
  • Respiratory System
  • Mice, Mutant Strains
  • Mice
  • Marfan Syndrome
  • Heart Ventricles
  • Echocardiography
  • Disease Progression
  • Disease Models, Animal