Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm
Mild aerobic exercise blocks elastin fiber fragmentation and aortic dilatation in a mouse model of Marfan syndrome associated aortic aneurysm
复制标题
DOI：
10.1152/japplphysiol.00132.2017
复制
发表时间：
2017-07-01
影响因子：
3.3
通讯作者：
Esfandiarei, Mitra
中科院分区：
文献类型：
--
作者：
Gibson, Christine;Nielsen, Cory;Esfandiarei, Mitra
马凡氏综合征（一种由纤维蛋白-1基因杂合突变引起的结缔组织疾病）患者通常允许进行常规的低强度体力活动。然而，身高高于平均水平鼓励患有马凡氏综合征的年轻人从事高强度的接触性运动，不幸的是，这增加了患主动脉瘤和破裂的风险，这是马凡氏综合征患者死亡的主要原因。在这项研究中，我们研究了不同强度的自愿（笼轮）或强迫（跑步机）有氧运动对马凡氏综合征小鼠模型主动脉功能和结构的影响。四周大的马凡小鼠和野生型小鼠分别接受自愿和强制运动方案或久坐生活方式5个月。胸主动脉组织分离并进行结构和功能研究。我们的数据显示，运动改善了马凡小鼠的主动脉壁结构和功能，并且有益效果是双相的，在低强度运动（55-65% VO2max）时效果最佳，在高强度运动（85% VO2max）时效果逐渐减弱。马凡氏小鼠弹性蛋白断裂减少的机制与主动脉壁内基质金属蛋白酶2和9的表达减少有关。这些发现首次证明了轻度运动对马凡氏综合征相关动脉瘤主动脉壁结构完整性的潜在有益影响。我们的研究发现，适度但不剧烈的运动可以保护马凡氏综合征小鼠模型的主动脉结构和功能，这可能对年轻马凡氏综合征患者的医疗护理具有重要意义。
Regular lowimpact 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 highintensity 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% V O-2max) and tapering off at a higher intensity of exercise (85% VO2max). 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.