Gut Metabolite Indole-3-Propionic Acid Regulates Macrophage Autophagy Through PPT1 Inhibiting Aging-Related Myocardial Fibrosis.

Jing Lu, Hongyan Wang, Haiyu Zhang, Jiahao Li, Hanqi Li, Qiuyu Chen, Dongyu Han, Jialiang Liu, Lin Lv, Jie Xiong, Keying Yuan, Xianpeng Wei, Siqi Sheng, Fukai Liu, Yuanqi Shi, Zengxiang Dong, Yue Li

Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China.Department of Pharmacy, The First Affiliated Hospital of Harbin Medical University, Harbin, 150000, China. · pubmed

Paper

Abstract

Cardiac fibrosis, a key pathological feature of cardiac remodeling, is a major contributor to mortality in older patients with heart failure. The underlying mechanisms are complex, involving alterations in intercellular communication and chronic inflammation. This study investigates the role of indole-3-propionic acid (IPA) in aging-related myocardial fibrosis and its regulatory effects on autophagy through palmitoyl-protein thioesterase 1 (PPT1). Here, plasma levels of IPA, a tryptophan-derived metabolite, are found to be reduced in older patients with heart failure, and this reduction is associated with deteriorating cardiac function. Notably, IPA supplementation significantly attenuated aging-related myocardial fibrosis. PPT1, a lysosomal enzyme involved in autophagy, is upregulated in macrophages during aging. IPA reversed aging-induced increase in PPT1 expression. Using PPT1

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Research summary

Indole-3-propionic acid supplementation can attenuate aging-related myocardial fibrosis by regulating macrophage autophagy through PPT1 inhibition. This study addresses a mechanism related to aging and its impact on cardiac health, which is crucial for understanding and potentially mitigating age-related diseases.

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