Tricaprin can prevent the development of AAA by attenuating aortic degeneration

Hirona Kugo; Yuki Sugiura; Rena Fujishima; Shintou Jo; Hirotaka Mishima; Erina Sugamoto; Hiroki Tanaka; Satoshi Yamaguchi; Yoshihiko Ikeda; Ken-Ichi Hirano; Tatsuya Moriyama; Nobuhiro Zaima

doi:10.1016/j.biopha.2023.114299

Tricaprin can prevent the development of AAA by attenuating aortic degeneration

Biomed Pharmacother. 2023 Apr:160:114299. doi: 10.1016/j.biopha.2023.114299. Epub 2023 Jan 30.

Authors

Affiliations

¹ Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan.
² Department of Biochemistry, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan.
³ Department of Medical Physiology, Hamamatsu University School of Medicine, Hamamatsu 431-3192, Japan.
⁴ Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Department of Triglyceride Science, Graduate School of Medicine, Osaka University, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan.
⁵ Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Department of Triglyceride Science, Graduate School of Medicine, Osaka University, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan; Department of Pathology, National Cerebral and Cardiovascular Center, Suita, Osaka 564-8565, Japan.
⁶ Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan; Agricultural Technology and Innovation Research Institute, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan.
⁷ Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan; Agricultural Technology and Innovation Research Institute, Kindai University, 204-3327 Nakamachi, Nara City, Nara 631-8505, Japan. Electronic address: zaima@nara.kindai.ac.jp.

PMID: 36724640
DOI: 10.1016/j.biopha.2023.114299

Abstract

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.

Keywords: Abdominal aortic aneurysm; Hypoperfusion; Matrix metalloproteinase; Medium-chain triglycerides; Smooth muscle cell; Tricaprin.

MeSH terms

Animals
Aorta, Abdominal* / metabolism
Aortic Aneurysm, Abdominal* / metabolism
Collagen / metabolism
Disease Models, Animal
Elastin / metabolism
Rats
Triglycerides / metabolism

Substances

tricaprin
Elastin
Triglycerides
Collagen