Spermidine Enhances Mitochondrial Function and Mitigates Aortic Valve Calcification
Aortic stenosis (AS) is a severe heart valve disease marked by calcification, leading to heart failure. This study examined mitochondrial function in human aortic valve interstitial cells isolated from patients with AS and tested spermidine, an autophagy inducer as AS treatment. Spermidine treatment reduced fibrosis and calcification in human aortic valve interstitial cells and improved these features in spermidine-treated mice. The AKT-TP53-DNMT1-PPARG pathway was implicated, and DNA methyltransferase 1 inhibition by 5-azacytidine enhanced mitochondrial biogenesis by reducing mitochondrial DNA hypermethylation. These findings suggest that spermidine or DNA methyltransferase 1 inhibition could prevent aortic valve disease by improving mitochondrial function.
Authors
- Jeong Eun Yu
- Kyoung‐Hee Choi (ORCID: https://orcid.org/0000-0001-7778-2053)
- Duk‐Hyun Kang (ORCID: https://orcid.org/0000-0003-4031-8649)
- Naaleum Song (ORCID: https://orcid.org/0000-0002-2278-7698)
- Sahmin Lee (ORCID: https://orcid.org/0000-0003-2250-7948)
- Kyunggon Kim (ORCID: https://orcid.org/0000-0002-3072-5331)
- Jae‐Kwan Song (ORCID: https://orcid.org/0000-0002-6469-801X)
- Elena Aïkawa (ORCID: https://orcid.org/0000-0001-7835-2135)
- Jong‐Min Song (ORCID: https://orcid.org/0000-0002-6754-8199)
- Eunhye Ji (ORCID: https://orcid.org/0000-0002-6274-8730)
- Dae‐Hee Kim (ORCID: https://orcid.org/0000-0002-8275-4871)
- Jiyoung Yu (ORCID: https://orcid.org/0000-0002-3953-200X)
Institutions
- Ulsan College (KR)
- Brigham and Women's Hospital (US)
- Asan Medical Center (KR)
- University of Ulsan (KR)
Publication Details
- Journal
- JACC Basic to Translational Science
- Published
- 2025-02-12
- DOI
- https://doi.org/10.1016/j.jacbts.2024.11.011
- Citations
- 9
- Primary Topic
- Fuel Cells and Related Materials
- Type
- article
- Field-Weighted Citation Impact
- 6.57