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

2017 ◽  
Vol 123 (1) ◽  
pp. 147-160 ◽  
Author(s):  
Christine Gibson ◽  
Cory Nielsen ◽  
Ramona Alex ◽  
Kimbal Cooper ◽  
Michael Farney ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Mouse Model ◽  
Aerobic Exercise ◽  
Marfan Syndrome ◽  
Aortic Wall ◽  
Clinical Care ◽  
Structure And Function ◽  
Strenuous Exercise ◽  
Aortic Dilatation ◽  
And Function

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.

scholarly journals Long-term effects of losartan on structure and function of the thoracic aorta in a mouse model of Marfan syndrome

2009 ◽  
Vol 158 (6) ◽  
pp. 1503-1512 ◽  
Author(s):  
HH Clarice Yang ◽  
Jong Moo Kim ◽  
Elliott Chum ◽  
Cornelis van Breemen ◽  
Ada WY Chung
Keyword(s):  
Mouse Model ◽  
Marfan Syndrome ◽  
Thoracic Aorta ◽  
Structure And Function ◽  
Long Term Effects ◽  
And Function

Glutathione system participation in thoracic aneurysms from patients with Marfan syndrome

VASA ◽  
2017 ◽  
Vol 46 (3) ◽  
pp. 177-186 ◽  
Author(s):  
Alejandra María Zúñiga-Muñoz ◽  
Israel Pérez-Torres ◽  
Verónica Guarner-Lans ◽  
Elías Núñez-Garrido ◽  
Rodrigo Velázquez Espejel ◽  
...  
Keyword(s):  
Aortic Aneurysm ◽  
Marfan Syndrome ◽  
Aortic Aneurysms ◽  
Aortic Dilatation ◽  
Glutathione S Transferase ◽  
Reduced And Oxidized Glutathione ◽  
Total Antioxidant ◽  
Elevated Activity ◽  
Acute Dissection ◽  
Thoracic Aneurysms

Abstract. Background: Aortic dilatation in Marfan syndrome (MFS) is progressive. It is associated with oxidative stress and endothelial dysfunction that contribute to the early acute dissection of the vessel and can result in rupture of the aorta and sudden death. We evaluated the participation of the glutathione (GSH) system, which could be involved in the mechanisms that promote the formation and progression of the aortic aneurysms in MFS patients. Patients and methods: Aortic aneurysm tissue was obtained during chest surgery from eight control subjects and 14 MFS patients. Spectrophotometrical determination of activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), glutathione reductase (GR), lipid peroxidation (LPO) index, carbonylation, total antioxidant capacity (TAC), and concentration of reduced and oxidized glutathione (GSH and GSSG respectively), was performed in the homogenate from aortic aneurysm tissue. Results: LPO index, carbonylation, TGF-β1, and GR activity were increased in MFS patients (p < 0.04), while TAC, GSH/GSSG ratio, GPx, and GST activity were significantly decreased (p < 0.04). Conclusions: The depletion of GSH, in spite of the elevated activity of GR, not only diminished the activity of GSH-depend GST and GPx, but increased LPO, carbonylation and decreased TAC. These changes could promote the structural and functional alterations in the thoracic aorta of MFS patients.

XIAP gene therapy effects on retinal ganglion cell structure and function in a mouse model of glaucoma

Gene Therapy ◽  
2021 ◽  
Author(s):  
Shagana Visuvanathan ◽  
Adam N. Baker ◽  
Pamela S. Lagali ◽  
Stuart G. Coupland ◽  
Garfield Miller ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Mouse Model ◽  
Ganglion Cell ◽  
Retinal Ganglion Cell ◽  
Cell Structure ◽  
Structure And Function ◽  
Retinal Ganglion ◽  
And Function

Localized Administration of Doxycycline Suppresses Aortic Dilatation in an Experimental Mouse Model of Abdominal Aortic Aneurysm

2006 ◽  
Vol 20 (2) ◽  
pp. 228-236 ◽  
Author(s):  
Michel A. Bartoli ◽  
Federico E. Parodi ◽  
Jack Chu ◽  
Monica B. Pagano ◽  
Dongli Mao ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Mouse Model ◽  
Aortic Dilatation ◽  
Abdominal Aortic ◽  
Experimental Mouse Model ◽  
Experimental Mouse

scholarly journals Oxytocin antagonism prevents pregnancy-associated aortic dissection in a mouse model of Marfan syndrome

2019 ◽  
Vol 11 (490) ◽  
pp. eaat4822 ◽  
Author(s):  
Jennifer Pardo Habashi ◽  
Elena Gallo MacFarlane ◽  
Rustam Bagirzadeh ◽  
Caitlin Bowen ◽  
Nicholas Huso ◽  
...  
Keyword(s):  
Aortic Dissection ◽  
Mouse Model ◽  
Marfan Syndrome ◽  
Uterine Contraction ◽  
Aortic Wall ◽  
Erk Activation ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Erk Kinase

Women with Marfan syndrome (MFS) are at high risk for pregnancy-associated aortic dissection. Pathogenic models that singularly invoke hemodynamic stress are difficult to reconcile with predominant postnatal occurrence of aortic tear, often occurring weeks to months after delivery. In consideration of events that peak at term, are sustained after delivery, and might synergize with previously defined signaling pathways implicated in aneurysm progression, we examined the hormone oxytocin, which initiates uterine contraction and milk letdown for the duration of lactation through phosphorylation of extracellular signal–regulated kinase (ERK). In a mouse model of MFS that shows highly penetrant postnatal aortic dissection, risk was strongly attenuated by preventing lactation or use of an oxytocin receptor antagonist. Survival correlated inversely with the extent of ERK activation in the aortic wall, and strong protection was observed upon attenuation of ERK phosphorylation using an inhibitor of ERK kinase (MEK) or the U.S. Food and Drug Administration–approved medication hydralazine, offering potential therapeutic strategies for pregnancy-associated vascular catastrophe in the setting of MFS.

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