Flow-Induced Reprogramming of Endothelial Cells (FIRE) in Atherosclerosis: From Mechanobiology to Therapeutics
Atherosclerosis is the major underlying cause of myocardial infarction and stroke. It occurs preferentially in arterial regions exposed to disturbed flow (d-flow) by mechanisms involving broad changes in the expression of coding and non-coding genes. Using the partial carotid ligation model of atherosclerosis in mice and gene array and "bulk" RNA sequencing studies, we revealed the roles of flow-sensitive genes and microRNAs in endothelial dysfunction and atherosclerosis. Furthermore, these results showed that targeting mechanosensitive genes and "athero-miRs" provide a new treatment paradigm in atherosclerosis. Recently, we carried out single-cell (sc)RNAseq and scATACseq studies using the partial carotid ligation model of atherosclerosis. The single-cell study results and additional validation studies revealed that d-flow reprograms endothelial cells to proatherogenic phenotypes, including EndMT and endothelial-to-immune cell-like transition. The scRNAseq study revealed several novel flow-sensitive genes and pathways, further characterized to define how flow regulates endothelial reprogramming and atherosclerosis. By targeting those flow-sensitive genes, we have been developing novel anti-atherogenic therapeutics. I will also discuss novel targeted RNA therapeutic approaches to treat atherosclerosis.
Hosted by Professor KiBum Lee
~Coffee/tea will be served prior to the lecture~