Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosis Article Swipe
Laura Boccuni
,
Frieda Marka
,
Manuel Salzmann
,
Alessia Schirripa
,
Elisabeth Ableitner
,
Magdalena Siller
,
Mira Brekalo
,
Patrick Haider
,
Stefan Stojković
,
Christoph Neumayer
,
Tiit Örd
,
Karoline Kollmann
,
Alice Assinger
,
Thomas Decker
,
Thomas Köcher
,
Michael B. Fischer
,
Marion Mußbacher
,
Andreas Bergthaler
,
Christian Hengstenberg
,
Bruno K. Podesser
,
Minna U. Kaikkonen
,
Johann Wojta
,
Philipp J. Hohensinner
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adw9952
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1126/sciadv.adw9952
Macrophage-to-foam cell transition is an integral part of atherosclerotic plaque progression. Particularly, oxidized low-density lipoprotein (oxLDL) is a driving factor in foam cell formation, altering macrophage function and metabolism. The aim of our research was to understand the impact of oxLDL-induced mitochondrial reactive oxygen species on macrophage-to-foam cell differentiation. We demonstrate that macrophage oxLDL-derived superoxide modulates mitochondrial metabolic reprogramming, facilitating foam cell formation. Mechanistically, mitochondrial superoxide drives signal transducers and activators of transcription 5 (STAT5) activation, leading to reduced tricarboxylic acid cycle activity. In parallel, mitochondrial superoxide enhances chromatin accessibility at STAT5 target genes, establishing a distinct STAT5 signaling signature in foam cells ex vivo and in human and mouse plaques in vivo. Inhibition of STAT5 during atherosclerosis progression prevents the differentiation of macrophages to mature Trem2 hi Gpnmb hi foam cells. Collectively, our data describe an oxLDL-induced, mitochondrial superoxide–dependent STAT5 activation that leads to a self-amplifying feedback loop of reciprocal mitochondrial superoxide production and STAT5 activation, ultimately driving macrophage-to-foam cell transition.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1126/sciadv.adw9952
- OA Status
- gold
- References
- 74
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4413755993
All OpenAlex metadata
Raw OpenAlex JSON
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https://openalex.org/W4413755993Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1126/sciadv.adw9952Digital Object Identifier
- Title
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Mitochondrial ROS drive foam cell formation via STAT5 signaling in atherosclerosisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-08-27Full publication date if available
- Authors
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Laura Boccuni, Frieda Marka, Manuel Salzmann, Alessia Schirripa, Elisabeth Ableitner, Magdalena Siller, Mira Brekalo, Patrick Haider, Stefan Stojković, Christoph Neumayer, Tiit Örd, Karoline Kollmann, Alice Assinger, Thomas Decker, Thomas Köcher, Michael B. Fischer, Marion Mußbacher, Andreas Bergthaler, Christian Hengstenberg, Bruno K. Podesser, Minna U. Kaikkonen, Johann Wojta, Philipp J. HohensinnerList of authors in order
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https://doi.org/10.1126/sciadv.adw9952Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1126/sciadv.adw9952Direct OA link when available
- Concepts
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Foam cell, Cell biology, Mitochondrion, Cell, Chemistry, Mitochondrial ROS, Biology, Biochemistry, Lipoprotein, CholesterolTop concepts (fields/topics) attached by OpenAlex
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0Total citation count in OpenAlex
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74Number of works referenced by this work
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10Other works algorithmically related by OpenAlex
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