Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm
| Autor: | Brajesh K. Lal, Jackie Zhang, Vicki L. Gray, Areck A. Ucuzian, Dudley K. Strickland, Brittany O. Aicher, Rebeca Galisteo, Selen C. Muratoglu, Allison L. Arai |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty MMP3 Physiology Aortic Rupture Lysyl oxidase Aorta Thoracic Vascular Remodeling Thoracic aortic aneurysm Aortic aneurysm Aneurysm Physiology (medical) Internal medicine medicine Aerobic exercise Animals Aortic dissection Extracellular Matrix Proteins biology Aortic Aneurysm Thoracic business.industry Hemodynamics medicine.disease Exercise Therapy Extracellular Matrix Mice Inbred C57BL Aortic Dissection Disease Models Animal Gene Expression Regulation Aminopropionitrile Proteolysis biology.protein Cardiology Disease Progression Cardiology and Cardiovascular Medicine business Elastin Research Article Dilatation Pathologic Signal Transduction |
| Zdroj: | Am J Physiol Heart Circ Physiol |
| Popis: | Thoracic aortic aneurysm and dissection (TAAD) is a deadly disease characterized by intimal disruption induced by hemodynamic forces of the circulation. The effect of exercise in patients with TAAD is largely unknown. β-Aminopropionitrile (BAPN) is an irreversible inhibitor of lysyl oxidase that induces TAAD in mice. The objective of this study was to investigate the effect of aerobic exercise on BAPN-induced TAAD. Upon weaning, mice were given either BAPN-containing water or standard drinking water and subjected to either conventional cage activity (BAPN-CONV) or forced treadmill exercise (BAPN-EX) for up to 26 wk. Mortality was 23.5% (20/85) for BAPN-CONV mice versus 0% (0/22) for BAPN-EX mice (hazard ratio 3.8; P = 0.01). BAPN induced significant elastic lamina fragmentation and intimal-medial thickening compared with BAPN-untreated controls, and aneurysms were identified in 50% (5/10) of mice that underwent contrast-enhanced CT scanning. Exercise significantly decreased BAPN-induced wall thickening, calculated circumferential wall tension, and lumen diameter, with 0% (0/5) of BAPN-EX demonstrating chronic aortic aneurysm formation on CT scan. Expression of selected genes relevant to vascular diseases was analyzed by qRT-PCR. Notably, exercise normalized BAPN-induced increases in TGF-β pathway-related genes Cd109, Smad4, and Tgfβr1; inflammation-related genes Vcam1, Bcl2a1, Ccr2, Pparg, Il1r1, Il1r1, Itgb2, and Itgax; and vascular injury- and response-related genes Mmp3, Fn1, and Vwf. Additionally, exercise significantly increased elastin expression in BAPN-treated animals compared with controls. This study suggests that moderate aerobic exercise may be safe and effective in preventing the most devastating outcomes in TAAD. NEW & NOTEWORTHY Moderate aerobic exercise was shown to significantly reduce mortality, extracellular matrix degradation, and thoracic aortic aneurysm and dissection formation associated with lysyl oxidase inhibition in a mouse model. Gene expression suggested a reversal of TGF-β, inflammation, and extracellular matrix remodeling pathway dysregulation, along with augmented elastogenesis with exercise. |
| Databáze: | OpenAIRE |
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