title: 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 (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% V̇o2max) and tapering off at a higher intensity of exercise (85% V̇o2max). 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.NEW & NOTEWORTHYThe 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.
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Christine
authors.initials: C
authors.lastname: Gibson
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Cory
authors.initials: C
authors.lastname: Nielsen
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Ramona
authors.initials: R
authors.lastname: Alex
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Kimbal
authors.initials: K
authors.lastname: Cooper
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Michael
authors.initials: M
authors.lastname: Farney
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gaufin
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Jason Z
authors.initials: JZ
authors.lastname: Cui
authors.affiliation: Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van Breemen
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona; and.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Broderick
authors.affiliation: Department of Physiology, Arizona College of Osteopathic Medicine, Midwestern University, Glendale, Arizona; and.
authors.forename: Johana
authors.initials: J
authors.lastname: Vallejo-Elias
authors.affiliation: Department of Biomedical Sciences, College of Health Sciences; mesfan@midwestern.edu.|Department of Anesthesiology, Pharmacology, and Therapeutics, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Mitra
authors.initials: M
authors.lastname: Esfandiarei
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism / Q000503:physiopathology; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D004108:Dilatation, Pathologic / Q000503:physiopathology / Q000534:rehabilitation; D004195:Disease Models, Animal; D004548:Elasticity / Q000502:physiology*; D004549:Elastin / Q000378:metabolism; D008297:Male; D008382:Marfan Syndrome / Q000378:metabolism / Q000503:physiopathology / Q000534:rehabilitation*; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal / Q000379:methods* / Q000502:physiology
chemical_list: D004549:Elastin; D020778:Matrix Metalloproteinase 2
keywords: Marfan syndrome; aortic aneurysm; aortic elasticity; elastin fragmentation; mild exercise