Endothelial cells were isolated from pulmonary artery (CF-PAEC) of explanted CF lungs and CFTR activity was measured using patch clamping. With experiments under static condition or shear stress provocation, the study demonstrated that CF-PAEC reduced monolayer integrity and transendothelial electric resistance (TEER); further, a high number of microvescicles (EMV) was released. EMV were increased in peripheral blood of CF patients and inversely correlated with respiratory indices. In attempt to uncover molecular signatures of CFTR dysfunction in EC, they evaluated microRNA expression in CF-PAEC, identifying some microRNA overexpressed and others with low amount. Agents that increase cAMP levels such as phosphodiesterase inhibitors and beta adrenergic receptor agonists corrected TEER and monolayer integrity of CF-PAEC. These results encourage further studies on miRNA and transcellular communication pathways as well on the clinical utility of cAMP increasing drugs to correct the endothelial dysfunction in CF.