Cardiovascular Benefits of Moderate Exercise Training in Marfan Syndrome: Insights From an Animal Model

J Am Heart Assoc. 2017 Sep 25;6(9):e006438. doi: 10.1161/JAHA.117.006438.

Abstract

Background: Marfan syndrome (MF) leads to aortic root dilatation and a predisposition to aortic dissection, mitral valve prolapse, and primary and secondary cardiomyopathy. Overall, regular physical exercise is recommended for a healthy lifestyle, but dynamic sports are strongly discouraged in MF patients. Nonetheless, evidence supporting this recommendation is lacking. Therefore, we studied the role of long-term dynamic exercise of moderate intensity on the MF cardiovascular phenotype.

Methods and results: In a transgenic mouse model of MF (Fbn1C1039G/+), 4-month-old wild-type and MF mice were subjected to training on a treadmill for 5 months; sedentary littermates served as controls for each group. Aortic and cardiac remodeling was assessed by echocardiography and histology. The 4-month-old MF mice showed aortic root dilatation, elastic lamina rupture, and tunica media fibrosis, as well as cardiac hypertrophy, left ventricular fibrosis, and intramyocardial vessel remodeling. Over the 5-month experimental period, aortic root dilation rate was significantly greater in the sedentary MF group, compared with the wild-type group (∆mm, 0.27±0.07 versus 0.13±0.02, respectively). Exercise significantly blunted the aortic root dilation rate in MF mice compared with sedentary MF littermates (∆mm, 0.10±0.04 versus 0.27±0.07, respectively). However, these 2 groups were indistinguishable by aortic root stiffness, tunica media fibrosis, and elastic lamina ruptures. In MF mice, exercise also produced cardiac hypertrophy regression without changes in left ventricular fibrosis.

Conclusions: Our results in a transgenic mouse model of MF indicate that moderate dynamic exercise mitigates the progression of the MF cardiovascular phenotype.

Keywords: Marfan syndrome; aortic disease; endurance exercise; fibrosis; myocardiopathy.

MeSH terms

  • Animals
  • Aorta / pathology
  • Aorta / physiopathology
  • Aortic Aneurysm / genetics
  • Aortic Aneurysm / pathology
  • Aortic Aneurysm / physiopathology
  • Aortic Aneurysm / prevention & control*
  • Aortic Dissection / genetics
  • Aortic Dissection / pathology
  • Aortic Dissection / physiopathology
  • Aortic Dissection / prevention & control*
  • Cardiomyopathies / genetics
  • Cardiomyopathies / pathology
  • Cardiomyopathies / physiopathology
  • Cardiomyopathies / prevention & control*
  • Dilatation, Pathologic
  • Disease Models, Animal
  • Disease Progression
  • Exercise Therapy*
  • Female
  • Fibrillin-1 / genetics
  • Fibrosis
  • Genetic Predisposition to Disease
  • Male
  • Marfan Syndrome / genetics
  • Marfan Syndrome / pathology
  • Marfan Syndrome / physiopathology
  • Marfan Syndrome / therapy*
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Phenotype
  • Physical Conditioning, Animal / methods*
  • Sex Factors
  • Time Factors
  • Vascular Remodeling
  • Ventricular Function, Left
  • Ventricular Remodeling

Substances

  • Fibrillin-1