S-EPMC10521798 - Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques. - OmicsDI

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Dataset Information

Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.

ABSTRACT:

Background

Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown.

Methods

Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based on sex bias, relevance for smooth muscle biology, and coronary artery disease genetic enrichment. Network expression was linked to histologically determined plaque phenotypes. In addition, their expression in plaque cell types was studied at single-cell resolution using single-cell RNAseq. Finally, their relevance for disease progression was studied in female and male Apoe^-/- mice fed a Western diet for 18 and 30 weeks.

Results

Here, we identify multiple sex-stratified gene regulatory networks from human carotid atherosclerotic plaques. Prioritization of the female networks identified 2 main SMC gene regulatory networks in late-stage atherosclerosis. Single-cell RNA sequencing mapped these female networks to 2 SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like network was mostly expressed in plaques that were vulnerable in women. Finally, the mice ortholog of key driver gene MFGE8 (milk fat globule EGF and factor V/VIII domain containing) showed retained expression in advanced plaques from female mice but was downregulated in male mice during atherosclerosis progression.

Conclusions

Female atherosclerosis is characterized by gene regulatory networks that are active in fibrous vulnerable plaques rich in myofibroblast-like SMCs.

SUBMITTER: Diez Benavente E

PROVIDER: S-EPMC10521798 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Female Gene Networks Are Expressed in Myofibroblast-Like Smooth Muscle Cells in Vulnerable Atherosclerotic Plaques.

Diez Benavente Ernest E Karnewar Santosh S Buono Michele M Mili Eloi E Hartman Robin J G RJG Kapteijn Daniek D Slenders Lotte L Daniels Mark M Aherrahrou Redouane R Reinberger Tobias T Mol Barend M BM de Borst Gert J GJ de Kleijn Dominique P V DPV Prange Koen H M KHM Depuydt Marie A C MAC de Winther Menno P J MPJ Kuiper Johan J Björkegren Johan L M JLM Erdmann Jeanette J Civelek Mete M Mokry Michal M Owens Gary K GK Pasterkamp Gerard G den Ruijter Hester M HM

Arteriosclerosis, thrombosis, and vascular biology 20230817 10

<h4>Background</h4>Women presenting with coronary artery disease more often present with fibrous atherosclerotic plaques, which are currently understudied. Phenotypically modulated smooth muscle cells (SMCs) contribute to atherosclerosis in women. How these phenotypically modulated SMCs shape female versus male plaques is unknown.<h4>Methods</h4>Gene regulatory networks were created using RNAseq gene expression data from human carotid atherosclerotic plaques. The networks were prioritized based ...[more]

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