Genetic Recording of Transient Endothelial Activation in Distinct Alveolar Capillary Cells during Pulmonary Fibrosis

Endothelial to mesenchymal transition (EndoMT) is essential for embryonic development. However, the contribution of ECs to fibroblasts through EndoMT remains highly controversial in adult pathological conditions. Here, our dual-recombinase genetic system precisely captured extensive mesenchymal gene activation events of alveolar capillary cells in chronic TAC-induced pulmonary hypertension and fibrosis. Moreover, this type of endothelial activation was specifically observed in Plvap+ gCap, but not CAR4+ aCap capillary cells. In addition, our genetic tool confirmed the contribution of resident fibroblasts to pulmonary fibrosis. Unraveling the process of endothelial activation provides novel insights into potential therapeutic strategies targeting heart failure-induced pulmonary fibrosis. Overall design: In this study, we employed a dual-genetic approach to capture aSMA activation in pulmonary endothelial cells during transverse aortic constriction (TAC)-induced pulmonary fibrosis in mice. Endothelial cells (ECs) were labeled as ZsGreen+ and once aSMA activation occurred, even transiently, the cell was labeled as tdTomato+. To investigate the significance of aSMA activation in ECs, we compared the gene expression patterns of ZsGreen+ ECs and tdTomato+ ECs using bulk RNA-seq.