Spermidine Enhances Mitochondrial Function and Mitigates Aortic Valve Calcification

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-03-01 DOI:10.1016/j.jacbts.2024.11.011

Naaleum Song PhD , Eunhye Ji PhD , Jeong Eun Yu BS , Kyoung-Hee Choi BS , Dae-Hee Kim MD, PhD , Jong-Min Song MD, PhD , Duk-Hyun Kang MD, PhD , Jae-Kwan Song MD, PhD , Jiyoung Yu PhD , Kyunggon Kim PhD , Sahmin Lee MD, PhD , Elena Aikawa MD, PhD

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引用次数: 0

Abstract

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.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.