Protein trafficking dysfunctions: Role in the pathogenesis of pulmonary arterial hypertension

摘要: AbstractEarlier electron microscopic data had shown that a hallmark of the vascular remodeling in pulmonary arterial hypertension (PAH) man and experimental models includes enlarged vacuolated endothelial smooth muscle cells with increased endoplasmic reticulum Golgi stacks lesions. In cell culture vivo experiments monocrotaline model, we observed disruption function intracellular trafficking trapping diverse vesicle tethers, SNAREs SNAPs membranes (PAECs) (PASMCs). Consequences included loss surface caveolin-1, hyperactivation STAT3, mislocalization eNOS reduced surface/caveolar NO hypo-S-nitrosylation trafficking-relevant proteins. Similar tether, SNARE SNAP dysfunctions were also hypoxic PAECs subjected to scavenging. Strikingly, hypo-NO state ...