Expression of nucleosome assembly protein 1 like1 determines the reparative capacity of pulmonary microvascular endothelial cells following exposure to cigarette smoke extract

Cigarette smoke causes endothelial cell dysfunction and death, which can lead to the loss of pulmonary capillaries and emphysema. We have shown that the highly proliferative capacity of pulmonary microvascular endothelial cells (PMVECs) is dictated by the expression of nucleosome assembly protein 1 like1 (NAP1L1). However, whether NAP1L1-enriched cells are necessary for restoring the endothelium after smoke-induced injury remains to be determined. We hypothesized that cigarette smoke extract (CSE) negatively affects fundamental PMVEC repair processes and that NAP1L1 determines the reparative capacity of PMVECs following exposure to CSE. To test this hypothesis, wildtype PMVECs and PMVECs engineered to express varying levels of NAP1L1 were treated with CSE. CSE treated PMVECs exhibited a dose dependent decrease in viability, proliferation, migration, and rate of barrier integrity restoration. Downregulation of NAP1L1 in PMVECs resulted in decreased viability and proliferation following CSE treatment and recovery, but did not affect PMVEC migration or barrier integrity.