Date of Award
Master of Interdisciplinary Studies (MIS)
Background: Aortic aneurysms and dissections (AD) are common in aging populations, and their development is tightly associated with vascular inflammation. Aortic dissection and rupture are associated with high mortality. Currently, there is no effective drug treatment for AD progression and rupture except surgical treatment. Although ketone bodies have an anti-inflammation effect, it remains unclear whether ketone restrains AD and the risk of rupture.
Methods: C57BL/6J mouse underwent β-aminopropionitrile (BAPN) treatment with drinking water for 28 days, followed by angiotensin II (Ang II) mini-pump implantation for 3 days to induce AD. Ketone-ester (KE) was administered in drinking water starting at 17days after initiation of BAPN treatment. There were four groups: Sham, BAPN+Ang II, BAPN+Ang II+KE 20 g/L, and BAPN+Ang II+KE 50 g/L. The blood ketone level was monitored by a Precision Xtra meter. Ultrasound was employed to measure the aorta strain.
Results: KE treatment (both 20 g/L and 50 g/L) reduced the incidence of both thoracic aortic dissection and abdominal aortic dissection. KE at 50 g/L increased the survival rate of BAPN plus AngII-treated mice. KE treatment did not reverse the Ang II-induced aortic stiffness demonstrated by reduced aorta strain. BAPN and KE did not affect mice weights, but Ang II slightly reduced the mouse body weight. BAPN and KE treatment had no effect on water consumption. These results suggest that ketone appears to decrease aortic dissection and risk of rupture and provides a potential therapeutic strategy for aortic dissection.
Ibrahim, Abdulgafar, "The Effect of Ketone on β-aminopropionitrile-induced Vascular Remodeling." Thesis, Georgia State University, 2022.