Kugo Hirona, Sugiura Yuki, Fujishima Rena, Jo Shintou, Mishima Hirotaka, Sugamoto Erina, Tanaka Hiroki, Yamaguchi Satoshi, Ikeda Yoshihiko, Hirano Ken-Ichi, Moriyama Tatsuya, Zaima Nobuhiro
Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan.
Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan.
Biomed Pharmacother. 2023 Apr;160:114299. doi: 10.1016/j.biopha.2023.114299. Epub 2023 Jan 30.
Medical therapeutic options to prevent rupture of abdominal aortic aneurysm (AAA), a critical event, must be developed. Moreover, further understanding of the process of AAA development and rupture is crucial. Previous studies have revealed that aortic hypoperfusion can induce the development of AAA, and we successfully developed a hypoperfusion-induced AAA animal model. In this study, we examined the effects of medium-chain triglycerides (MCTs), tricaprylin (C8-TG) and tricaprin (C10-TG), on hypoperfusion-induced AAA rat model. We estimated the effects of MCTs on aortic pathologies, mechanical properties of the aorta, and development of AAA. C10-TG, but not C8-TG, significantly suppressed AAA development and completely prevented the rupture. We observed that C10-TG prevented the development and rupture of AAA, but not C8-TG. Additionally, regression of AAA diameter was observed in the C10-TG group. Pathological analysis revealed C10-TG improved the hypoperfusion-induced increase in hypoxia-inducible factor-1α levels, medial smooth muscle cells (SMCs) loss, degeneration of aortic elastin and collagen fibers, and loss of aortic wall elasticity. In addition, regression of the formed AAA was observed by administration of C10-TG after AAA formation. C10-TG administration after AAA formation improved degeneration of AAA wall including degradation of aortic elastin and collagen fibers, stenosis of vasa vasorum, and loss of medial SMCs. These data suggest C10-TG can prevent AAA by attenuating aortic hypoperfusion and degeneration. Considering the clinical safety of C10-TG, C10-TG can be a promising AAA drug candidate.
必须开发出预防腹主动脉瘤（AAA）破裂这一关键事件的医学治疗方案。此外，进一步了解AAA的发生和破裂过程至关重要。先前的研究表明，主动脉低灌注可诱发AAA的发生，我们成功建立了低灌注诱导的AAA动物模型。在本研究中，我们研究了中链甘油三酯（MCTs）、三辛酸甘油酯（C8-TG）和三癸酸甘油酯（C10-TG）对低灌注诱导的AAA大鼠模型的影响。我们评估了MCTs对主动脉病变、主动脉力学性能和AAA发生的影响。C10-TG而非C8-TG能显著抑制AAA的发生并完全防止其破裂。我们观察到C10-TG可预防AAA的发生和破裂，但C8-TG不能。此外，在C10-TG组观察到AAA直径缩小。病理分析显示，C10-TG改善了低灌注诱导的缺氧诱导因子-1α水平升高、中膜平滑肌细胞（SMC）丢失、主动脉弹性蛋白和胶原纤维变性以及主动脉壁弹性丧失。此外，在AAA形成后给予C10-TG可观察到已形成的AAA缩小。AAA形成后给予C10-TG可改善AAA壁的变性，包括主动脉弹性蛋白和胶原纤维的降解、血管滋养管狭窄以及中膜SMC的丢失。这些数据表明，C10-TG可通过减轻主动脉低灌注和变性来预防AAA。考虑到C10-TG的临床安全性，C10-TG可能是一种有前景的抗AAA药物候选物。
