What is the clinical evidence from this study?

Study design: Observational. Population: End-stage atherosclerotic plaques (n=1889). Intervention: Female sex vs. Male sex. Primary outcome: Presence of fibrous lesions.

What question did this study set out to answer?

To investigate the molecular differences in atherosclerotic fibrous plaques between sexes.

February 8, 2026Circulation Research

Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β

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Key result

Female sex is linked to ~61% higher rates of fibrous plaques via SMC-driven ECM remodeling.

n=1,889

Population

1889 end-stage atherosclerotic plaques isolated from carotid endarterectomy patients included in the…

Design

Cohort

Authors

TSTim R. SakkersUtrecht University EMEloi MiliUtrecht University HWHanna WinterKlinikum rechts der Isar

Discussion

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Implication

Women and men with end-stage fibrous atherosclerotic plaques exhibit distinct molecular profiles, with female plaques characterized by TGF-β-driven ECM remodeling and male plaques by macrophage-mediated inflammation.

Key Points

To investigate the molecular differences in atherosclerotic fibrous plaques between sexes.
Isolated end-stage atherosclerotic plaques from carotid endarterectomy patients.
Conducted histological assessments and clinical characteristic linkage.
Analyzed protein, RNA, and DNA methylation data.
Performed spatial transcriptomics and gene expression localization.
Examined endothelial and vascular smooth muscle cell responses to TGF-β.
Fibrous plaques were found in 50% of females and 31% of males.
Female fibrous plaques showed increased ECM remodeling and TGF-β responses.
Men with fibrous plaques linked to higher diabetes prevalence and macrophage inflammation.
Endothelial-to-mesenchymal transition and ECM remodeling induced by TGF-β confirmed in vitro.
SMAD3 inhibition partially reversed female-biased molecular mechanisms.

Study Design

Type

Observational (n=1,889)

Structured PICO

Population

1,889 patients (30.7% female) undergoing carotid endarterectomy with end-stage atherosclerotic plaques from the Athero-Express Biobank.

Outcome

Sex-biased molecular and cellular mechanisms in histologically determined fibrous plaquessurrogate

Main Result

Absolute Event Rate: 50% vs 31%

Cite This Study

Sakkers et al. (2026) conducted an observational in End-stage atherosclerotic plaques (n=1,889). Female sex vs. Male sex was evaluated on Presence of fibrous lesions. Fibrous atherosclerotic plaques were observed in 50% of female patients compared to 31% of male patients, characterized by smooth muscle cell-driven ECM remodeling and TGF-β response in women.

synapsesocial.com/papers/698828cb0fc35cd7a88489cf https://doi.org/10.1161/circresaha.125.327624

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Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

Atherosclerotic Fibrous Plaques in Women Present ECM Remodeling Linked to TGF-β

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Main Result

Cite This Study

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