PIEZO1 targeting in macrophages boosts phagocytic activity and foam cell apoptosis in atherosclerosis.
Cell Mol Life Sci
; 81(1): 331, 2024 Aug 06.
Article
en En
| MEDLINE
| ID: mdl-39107572
ABSTRACT
The rising incidences of atherosclerosis have necessitated efforts to identify novel targets for therapeutic interventions. In the present study, we observed increased expression of the mechanosensitive calcium channel Piezo1 transcript in mouse and human atherosclerotic plaques, correlating with infiltration of PIEZO1-expressing macrophages. In vitro administration of Yoda1, a specific agonist for PIEZO1, led to increased foam cell apoptosis and enhanced phagocytosis by macrophages. Mechanistically, PIEZO1 activation resulted in intracellular F-actin rearrangement, elevated mitochondrial ROS levels and induction of mitochondrial fragmentation upon PIEZO1 activation, as well as increased expression of anti-inflammatory genes. In vivo, ApoE-/- mice treated with Yoda1 exhibited regression of atherosclerosis, enhanced stability of advanced lesions, reduced plaque size and necrotic core, increased collagen content, and reduced expression levels of inflammatory markers. Our findings propose PIEZO1 as a novel and potential therapeutic target in atherosclerosis.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Fagocitosis
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Apoptosis
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Aterosclerosis
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Células Espumosas
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Canales Iónicos
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Macrófagos
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Mol Life Sci
Asunto de la revista:
BIOLOGIA MOLECULAR
Año:
2024
Tipo del documento:
Article
País de afiliación:
Suecia