TY - UNPB
T1 - Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques
AU - Benavente, Ernest Diez
AU - Karnewar, Santosh
AU - Buono, Michele
AU - Mili, Eloi
AU - Hartman, Robin J G
AU - Kapteijn, Daniek
AU - Slenders, Lotte
AU - Daniels, Mark
AU - Aherrahrou, Redouane
AU - Reinberger, Tobias
AU - Mol, Barend M
AU - de Borst, Gert J
AU - de Kleijn, Dominique P V
AU - Prange, Koen H M
AU - Depuydt, Marie A C
AU - de Winther, Menno P J
AU - Kuiper, Johan
AU - Bj Rkegren, Johan L M
AU - Erdmann, Jeanette
AU - Civelek, Mete
AU - Mokry, Michal
AU - Owens, Gary K
AU - Pasterkamp, Gerard
AU - den Ruijter, Hester M
PY - 2023/2/9
Y1 - 2023/2/9
N2 - Women presenting with coronary artery disease (CAD) 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. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.
AB - Women presenting with coronary artery disease (CAD) 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. Here, we show sex-stratified gene regulatory networks (GRNs) from human carotid atherosclerotic tissue. Prioritization of these networks identified two main SMC GRNs in late-stage atherosclerosis. Single-cell RNA-sequencing mapped these GRNs to two SMC phenotypes: a phenotypically modulated myofibroblast-like SMC network and a contractile SMC network. The myofibroblast-like GRN was mostly expressed in plaques that were vulnerable in females. Finally, mice orthologs of the female myofibroblast-like genes showed retained expression in advanced plaques from female mice but were downregulated in male mice during atherosclerosis progression. Female atherosclerosis is driven by GRNs that promote a fibrous vulnerable plaque rich in myofibroblast-like SMCs.
U2 - 10.1101/2023.02.08.527690
DO - 10.1101/2023.02.08.527690
M3 - Preprint
C2 - 36798294
BT - Female gene networks are expressed in myofibroblast-like smooth muscle cells in vulnerable atherosclerotic plaques
PB - BioRxiv
ER -