Longevity & AgingDisturbed Blood Flow Plus High Cholesterol Turns Artery-Lining Cells Into Immune-Like and Foam Cells
Atherosclerosis forms preferentially where blood flow is disturbed, even though high cholesterol affects the whole body. Using a mouse partial carotid ligation model, researchers combined disturbed flow with PCSK9-induced hypercholesterolaemia and a Western diet. Single-cell RNA sequencing of 98,553 cells from 95 mice suggested a two-hit process. Disturbed flow alone partially reprograms endothelial cells toward inflammation, mesenchymal-like states and a partial immune-like state. With high cholesterol added, some endothelial cells appear to transition fully into immune-like cells and into foam-like cells resembling those from smooth muscle cells and macrophages. Genetic lineage-tracing in endothelial-specific confetti mice, cultured human aortic endothelial cells, and reanalysis of human plaque datasets with immunostaining supported these findings. The work offers a cell-level roadmap for targeting flow-sensitive pathways, though it remains largely preclinical.
