Effects of Voluntary Exercise on Progression of Aortic Aneurysm in a Mouse Model of Marfan Syndrome

Abstract

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.