Phytosterols (PS) and sterol oxidation products are key dietary factors influencing atherosclerosis besides cholesterol, although the mechanisms remain elusive. Recently, single-cell RNA sequencing (scRNA-seq) has revealed the heterogeneity of multiple cell types associated with complex pathogenesis in atherosclerosis development.
Methods and results
Here, we performed scRNA-seq to investigate the alterations in the aortic cells from ApoE−/− mice induced by diet-derived PS or two sterol oxidation products, phytosterols oxidation products (POPs) and cholesterol oxidation products (COPs). We identified four fibroblast subpopulations with different functions, and immunofluorescence demonstrated their spatial heterogeneity, providing evidence that suggested the transformation of smooth muscle cells (SMCs) and fibroblasts in atherosclerosis. The composition and gene expression profiles of aortic cells changed broadly in response to PS/COPs/POPs exposure. Notably, PS exhibited an atheroprotective effect where different gene expressions were mainly found in B cells. Exposure to COPs accelerated atherosclerosis and resulted in marked alternations in myofibroblast subpopulations and T cells, while POPs only altered fibroblast subpopulations and B cells.
Our data elucidates the effects of dietary PS/COPs/POPs on aortic cells during atherosclerosis development, especially on the newly identified fibroblast subpopulations.