Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence

Di-Yang Sun, Wen-Bin Wu, Jian-Jin Wu, Yu Shi, Jia-Jun Xu, Shen-Xi Ouyang, Chen Chi, Yi Shi, Qing-Xin Ji, Jin-Hao Miao, Jiang-Tao Fu, Jie Tong, Ping-Ping Zhang, Jia-Bao Zhang, Zhi-Yong Li, Le-Feng Qu (), Fu-Ming Shen (), Dong-Jie Li () and Pei Wang ()
Additional contact information
Di-Yang Sun: Second Military Medical University/Naval Medical University
Wen-Bin Wu: Second Military Medical University/Naval Medical University
Jian-Jin Wu: Naval Medical University/Second Military Medical University
Yu Shi: Tongji University School of Medicine
Jia-Jun Xu: Naval Medical University/Second Military Medical University
Shen-Xi Ouyang: Tongji University School of Medicine
Chen Chi: Tongji University School of Medicine
Yi Shi: Fudan University
Qing-Xin Ji: Tongji University School of Medicine
Jin-Hao Miao: Changzheng Hospital Affiliated Hospital of Naval Medical University/Second Military Medical University
Jiang-Tao Fu: Second Military Medical University/Naval Medical University
Jie Tong: Tongji University School of Medicine
Ping-Ping Zhang: Second Military Medical University/Naval Medical University
Jia-Bao Zhang: Second Military Medical University/Naval Medical University
Zhi-Yong Li: Second Military Medical University/Naval Medical University
Le-Feng Qu: Naval Medical University/Second Military Medical University
Fu-Ming Shen: Tongji University School of Medicine
Dong-Jie Li: Tongji University School of Medicine
Pei Wang: Second Military Medical University/Naval Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-22

Abstract: Abstract Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD+ loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD+ loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45823-w Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45823-w

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45823-w

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().