SCUBE1 Controls BMPR2-Relevant Pulmonary Endothelial Function: Implications for Diagnostic Marker Development in Pulmonary Arterial Hypertension.
JACC Basic Transl Sci
; 5(11): 1073-1092, 2020 Nov.
Article
em En
| MEDLINE
| ID: mdl-33294740
ABSTRACT
Utilizing publicly available ribonucleic acid sequencing data, we identified SCUBE1 as a BMPR2-related gene differentially expressed between induced pluripotent stem cell-endothelial cells derived from pulmonary arterial hypertension (PAH) patients carrying pathogenic BMPR2 mutations and control patients without mutations. Endothelial SCUBE1 expression was decreased by known triggers of PAH, and its down-regulation recapitulated known BMPR2-associated endothelial pathophenotypes in vitro. Meanwhile, SCUBE1 concentrations were reduced in plasma obtained from PAH rodent models and patients with PAH, whereas plasma concentrations were tightly correlated with hemodynamic markers of disease severity. Taken together, these data implicate SCUBE1 as a novel contributor to PAH pathogenesis with potential therapeutic, diagnostic, and prognostic applications.
BMP, bone morphogenetic protein; BMPR2; EC, endothelial cell; PAEC, pulmonary arterial endothelial cell; PAH, pulmonary arterial hypertension; PAP, pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RV, right ventricle; SCUBE1; WSPH, World Symposium on Pulmonary Hypertension; endothelium; iPSC-EC, induced pluripotent stem cell-endothelial cell; mPAP, mean pulmonary artery pressure; pulmonary hypertension
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1
Coleções:
01-internacional
Base de dados:
MEDLINE
Tipo de estudo:
Diagnostic_studies
/
Prognostic_studies
Idioma:
En
Revista:
JACC Basic Transl Sci
Ano de publicação:
2020
Tipo de documento:
Article