Use of electronic cigarettes (E-cig) is rapidly expanding, representing a major and largely undefined public health risk. There is a growing appreciation that E-cig has broad effects across organ systems and notably within the vasculature, raising concerns for cardiovascular risk. Here, we define, through use of controlled E-cig exposure systems for in vivo experiments, single cell RNA and ATAC sequencing, histological characterization, and culture of human coronary artery smooth muscle cells, that E-cig has a distinct effect on the vascular smooth muscle cell (SMC) and confers a proatherogenic phenotype. We observe E-cig to increase plaque size and calcification through regulating SMC gene programs facilitating a pro-chondrogenic cell state. E-cig activates the epigenomic landscape of the vascular SMC and reveals glutamatergic signaling as a key regulatory mechanism of effect. This work highlights the adverse effect of E-cig on the vascular wall and raises concern of E-cig to promote atherosclerosis risk.
Damiani et al. (Wed,) studied this question.