Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm

Abstract

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 (wheel-cage) 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 life-style for five months. 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% of VO2 max) and tapering off at a higher intensity of exercise (85% of VO2 max). The mechanism underlying the reduced elastin fragmentation in Marfan mice involved reduction of the expression of matrix metalloproteinase 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 MFS, could have important implications for the medical care of young Marfan patients.

Copyright © 2017, Journal of Applied Physiology.

KEYWORDS:

Aortic aneurysm; Aortic elasticity; Elastin fragmentation; Marfan Syndrome; Mild exercise