Instead, the most profound defect in total Rap1 (Rap1A + Rap1B), EC-specific KO (Rap1iΔEC) mice is endothelial dysfunction due to a decreased NO bioavailability defect, evidenced by impaired vasorelaxation defect ex vivo and hypertension in vivo (Lakshmikanthan et al., 2015). This evidence concerns the gene RAP1B and endothelial dysfunction.