Pro-ferroptotic signaling promotes arterial aging via vascular smooth muscle cell senescence
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Nature Communications - 15(2024), 1, Seite 22 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Di-Yang Sun [VerfasserIn] |
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| Links: |
doi.org [kostenfrei] |
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| Themen: |
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| doi: |
10.1038/s41467-024-45823-w |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
DOAJ091183456 |
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| 520 | |a 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. | ||
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| 700 | 0 | |a Jia-Jun Xu |e verfasserin |4 aut | |
| 700 | 0 | |a Shen-Xi Ouyang |e verfasserin |4 aut | |
| 700 | 0 | |a Chen Chi |e verfasserin |4 aut | |
| 700 | 0 | |a Yi Shi |e verfasserin |4 aut | |
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| 700 | 0 | |a Jin-Hao Miao |e verfasserin |4 aut | |
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| 700 | 0 | |a Fu-Ming Shen |e verfasserin |4 aut | |
| 700 | 0 | |a Dong-Jie Li |e verfasserin |4 aut | |
| 700 | 0 | |a Pei Wang |e verfasserin |4 aut | |
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