Injury-Induced Shedding of Extracellular Vesicles Depletes Endothelial Cells of Cav-1 (Caveolin-1) and Enables TGF-β (Transforming Growth Factor-β)-Dependent Pulmonary Arterial Hypertension.

ABSTRACT: Objective- To determine whether pulmonary arterial hypertension is associated with endothelial cell (EC)-Cav-1 (caveolin-1) depletion, EC-derived extracellular vesicle cross talk with macrophages, and proliferation of Cav-1 depleted ECs via TGF-β (transforming growth factor-β) signaling. Approach and Results- Pulmonary vascular disease was induced in Sprague-Dawley rats by exposure to a single injection of VEGFRII (vascular endothelial growth factor receptor II) antagonist SU5416 (Su) followed by hypoxia (Hx) plus normoxia (4 weeks each-HxSu model) and in WT (wild type; Tie2.Cre^-; Cav1 ^lox/lox) and EC- Cav1^-/- (Tie2.Cre⁺; Cav1 ^fl/fl) mice (Hx: 4 weeks). We observed reduced lung Cav-1 expression in the HxSu rat model in association with

SUBMITTER: Oliveira SDS 

PROVIDER: S-EPMC7297129 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature