Moderate aerobic exercise prevents matrix degradation and death in a mouse model of aortic dissection and aneurysm

• Published in: American journal of physiology. Heart and circulatory physiology 2021-05, Vol.320 (5), p.H1786-H1801
• Main Authors: Aicher, Brittany O, Zhang, Jackie, Muratoglu, Selen C, Galisteo, Rebeca, Arai, Allison L, Gray, Vicki L, Lal, Brajesh K, Strickland, Dudley K, Ucuzian, Areck A
• Format: Article
• Language: English
• Subjects: Aerobics; Aminopropionitrile; Aneurysms; Animals; Aorta; Aorta, Thoracic - metabolism; Aorta, Thoracic - pathology; Aorta, Thoracic - physiopathology; Aortic Aneurysm, Thoracic - chemically induced; Aortic Aneurysm, Thoracic - metabolism; Aortic Aneurysm, Thoracic - pathology; Aortic Aneurysm, Thoracic - therapy; Aortic aneurysms; Aortic dissection; Aortic Dissection - chemically induced; Aortic Dissection - metabolism; Aortic Dissection - pathology; Aortic Dissection - therapy; Aortic Rupture - chemically induced; Aortic Rupture - metabolism; Aortic Rupture - pathology; Aortic Rupture - prevention & control; Blood circulation; CCR2 protein; Computed tomography; Diameters; Dilatation, Pathologic; Disease Models, Animal; Disease Progression; Dissection; Drinking water; Elastin; Exercise; Exercise Therapy; Extracellular Matrix - metabolism; Extracellular Matrix - pathology; Extracellular Matrix Proteins - metabolism; Gene expression; Gene Expression Regulation; Genes; Hemodynamics; Inflammation; Interleukin 1; Lysyl oxidase; Male; Mice; Mice, Inbred C57BL; Monocyte chemoattractant protein 1; Peroxisome proliferator-activated receptors; Physical fitness; Proteolysis; Signal Transduction; Smad4 protein; Thickening; Thorax; Treadmills; Vascular diseases; Vascular Remodeling; Weaning
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00229.2020

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; = 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 , , and ; inflammation-related genes , , , , , , , and ; and vascular injury- and response-related genes , , and . 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. 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.