Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm
| Autor: | Mitra Esfandiarei, Ramona Alex, Tom L. Broderick, Christine P. Gibson, Michael Farney, Cornelis van Breemen, Johana Vallejo-Elias, Kimbal Cooper, Jason Z. Cui, Douglas Gaufin, Cory Nielsen |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Marfan syndrome Male medicine.medical_specialty Physiology Aorta Thoracic Mice Transgenic 030204 cardiovascular system & hematology Marfan Syndrome 03 medical and health sciences Aortic aneurysm Mice 0302 clinical medicine Aneurysm Physiology (medical) medicine.artery Internal medicine Physical Conditioning Animal Medicine Thoracic aorta Aerobic exercise Animals cardiovascular diseases Cause of death biology Aortic Aneurysm Thoracic business.industry medicine.disease Elasticity Surgery Elastin Mice Inbred C57BL Disease Models Animal 030104 developmental biology Exercise intensity biology.protein Cardiology Matrix Metalloproteinase 2 business Dilatation Pathologic |
| Zdroj: | Journal of applied physiology (Bethesda, Md. : 1985). 123(1) |
| ISSN: | 1522-1601 |
| Popis: | 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 & NOTEWORTHY 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. |
| Databáze: | OpenAIRE |
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