Secretory Carrier Membrane Protein 3 Knockdown Attenuates Hypoxic Pulmonary Hypertension Potentially Involving WW Domain-Containing E3 Ubiquitin Protein Ligase 1.

We aimed to investigate whether secretory carrier membrane protein 3 (SCAMP3) knockdown could attenuate hypoxic pulmonary hypertension (HPH) potentially involving WW domain-containing E3 ubiquitin protein ligase 1 (WWP1). Fifty mice were randomly assigned to a blank group, an HPH group, a small interference (si)-negative control (NC) group, a si-SCAMP3 group and a si-SCAMP3 + si-WWP1 group (n = 10 per group). Pulmonary function, right ventricular systolic pressure (RVSP) and the Fulton index [RV/(LV + S)] were measured. Hematoxylin-eosin staining was performed to evaluate pulmonary vascular morphology and the pulmonary vascular remodeling indexes were calculated. Compared with the normoxia group, the hypoxia group exhibited significantly increased SCAMP3 relative expression, OD450 value and SCAMP3 protein expression in HPASMCs, while the apoptosis rate and WWP1 protein expression were significantly decreased (P < 0.05). Compared with the hypoxia group, the hypoxia + si-SCAMP3 group showed significantly reduced SCAMP3 relative expression, OD450 value and SCAMP3 protein expression, but significantly increased apoptosis rate and WWP1 protein expression (P < 0.05). Compared with the hypoxia + si-SCAMP3 group, the hypoxia + si-SCAMP3 + si-WWP1 group exhibited partial restoration of SCAMP3 expression increased OD450 value and SCAMP3 protein expression, and decreased apoptosis rate and WWP1 protein expression (P < 0.05). These findings suggest that SCAMP3 knockdown may inhibit hypoxia-induced proliferation and promote apoptosis potentially involving WWP1, thereby alleviating pulmonary vascular remodeling in HPH mice.