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

• Published in: Journal of the American Heart Association Vol. 6; no. 9
• Main Authors: Mas‐Stachurska, Aleksandra, Siegert, Anna‐Maria, Batlle, Monsterrat, Gorbenko del Blanco, Darya, Meirelles, Thayna, Rubies, Cira, Bonorino, Fabio, Serra‐Peinado, Carla, Bijnens, Bart, Baudin, Julio, Sitges, Marta, Mont, Lluís, Guasch, Eduard, Egea, Gustavo
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.09.2017; Wiley
• Subjects: Aneurismes aòrtics; Aneurysm, Dissecting - genetics; Aneurysm, Dissecting - pathology; Aneurysm, Dissecting - physiopathology; Aneurysm, Dissecting - prevention & control; Animal models in research; Animals; Aorta - pathology; Aorta - physiopathology; Aortic Aneurysm - genetics; Aortic Aneurysm - pathology; Aortic Aneurysm - physiopathology; Aortic Aneurysm - prevention & control; Aortic aneurysms; aortic disease; Cardiomyopathies - genetics; Cardiomyopathies - pathology; Cardiomyopathies - physiopathology; Cardiomyopathies - prevention & control; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; endurance exercise; Exercici; Exercise; Exercise Therapy; Female; Fibrillin-1 - genetics; Fibrosis; Genetic diseases; Genetic Predisposition to Disease; Malalties hereditàries; Male; Marfan syndrome; Marfan Syndrome - genetics; Marfan Syndrome - pathology; Marfan Syndrome - physiopathology; Marfan Syndrome - therapy; Mice, Inbred C57BL; Mice, Transgenic; Models animals en la investigació; myocardiopathy; Original Research; Phenotype; Physical Conditioning, Animal - methods; Sex Factors; Time Factors; Vascular Remodeling; Ventricular Function, Left; Ventricular Remodeling; fibrosis; endurance exercise; myocardiopathy; Marfan syndrome; aortic disease
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.117.006438

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.