Regular low-impact physical activity is generally allowed in patients with Marfan syndrome, a connective tissue disorder caused by heterozygous mutations in the fibrillin-1 gene. However, being above average in height encourages young adults with this syndrome to engage in high-intensity contact sports, which unfortunately increases the risk for aortic aneurysm and rupture, the leading cause of death in Marfan syndrome. In this study, we investigated the effects of voluntary (cage-wheel) or forced (treadmill) aerobic exercise at different intensities on aortic function and structure in a mouse model of Marfan syndrome. Four-week-old Marfan and wild-type mice were subjected to voluntary and forced exercise regimens or sedentary lifestyle for 5 mo. Thoracic aortic tissue was isolated and subjected to structural and functional studies. Our data showed that exercise improved aortic wall structure and function in Marfan mice and that the beneficial effect was biphasic, with an optimum at low intensity exercise (55-65% V̇o) and tapering off at a higher intensity of exercise (85% V̇o). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinases 2 and 9 within the aortic wall. These findings present the first evidence of potential beneficial effects of mild exercise on the structural integrity of the aortic wall in Marfan syndrome associated aneurysm. Our finding that moderate, but not strenuous, exercise protects aortic structure and function in a mouse model of Marfan syndrome could have important implications for the medical care of young Marfan patients. The present study provides conclusive scientific evidence that daily exercise can improve aortic health in a mouse model of Marfan syndrome associated aortic aneurysm, and it establishes the threshold for the exercise intensity beyond which exercise may not be as protective. These findings establish a platform for a new focus on promoting regular exercise in Marfan patients at an optimum intensity and create a paradigm shift in clinical care of Marfan patients suffering from aortic aneurysm complications.

Aortic aneurysm is the leading cause of death in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin‐1 gene. MFS aneurysm is characterized by weakening of the aortic wall due to elastin fibers fragmentation and aortic aneurysm. The above‐average height and distinct physical features make young adults with MFS, desirable candidates for competitive sports; but little is known about the exercise limit at which they will be at risk for aortic rupture. On the other hand, voluntary cardiovascular exercise has been shown to have a protective effect on the aortic wall structure and function. In this study, we investigated whether a voluntary aerobic exercise routine would have any effects on structure and function of the aorta in a mouse model of MFS. Four‐week old MFS and control mice were subjected to voluntary wheel exercise or sedentary life‐style for five months. Aortic tissue were isolated at the age of 24‐weeks, and subjected to structural and functional studies using histological staining and myography. During the study period, running activity (Km/day) in MFS mice was reduced by 37 percent, as compared to control mice. However, compared to non‐exercise MFS mice, their aortic wall structure (elastin fibers organization) and blood vessel function (contractility and vasodilation) were significantly improved. These findings provide new insights into the potential protective effects of a mild exercise routine in Marfan patients, especially in young adults affected by cardiovascular complications and aortic aneurysm. This work was funded by Midwestern University Graduate Research Fund.