RT Journal Article
SR Electronic
T1 Plasma receptor tyrosine kinase RET in pulmonary arterial hypertension diagnosis and differentiation
JF ERJ Open Research
JO erjor
FD European Respiratory Society
SP 00037-2019
DO 10.1183/23120541.00037-2019
VO 5
IS 4
A1 Joanna Säleby
A1 Habib Bouzina
A1 Salaheldin Ahmed
A1 Jakob Lundgren
A1 Göran Rådegran
YR 2019
UL http://openres.ersjournals.com/content/5/4/00037-2019.abstract
AB Background Pulmonary arterial hypertension (PAH) is a serious disease exhibiting unspecific symptoms, as a result of which diagnosis is often delayed and prognosis is poor. The underlying pathophysiology includes vasoconstriction and remodelling of small pulmonary arteries. As receptor tyrosine kinases (RTKs) and their ligands have been shown to promote PAH remodelling, our aim was to evaluate if their plasma levels may be utilised to differentiate between various causes of pulmonary hypertension.Methods 28 biomarkers involved in RTK signalling were measured using proximity extension assays in venous plasma from patients with PAH (n=48), chronic thromboembolic pulmonary hypertension (CTEPH) (n=20), pulmonary hypertension due to diastolic (n=33) or systolic (n=36) heart failure and heart failure patients without pulmonary hypertension (n=15), as well as healthy controls (n=20).Results Plasma proto-oncogene tyrosine-protein kinase receptor Ret (RET) was decreased (p<0.04) in PAH compared with all disease groups and controls. RET generated a sensitivity of 64.6% and a specificity of 81.6% for detecting PAH from other disease groups. PAH and the other pulmonary hypertension groups showed elevated plasma tyrosine-protein kinase MER (p<0.01), vascular endothelial growth factor (VEGF)-A (p<0.02), VEGF-D (p<0.01), placental growth factor (p<0.01), amphiregulin (p<0.02), hepatocyte growth factor (p<0.01) and transforming growth factor-α (p<0.05) and decreased VEGF receptor-2 (p<0.04) and epidermal growth factor receptor (p<0.01) levels compared with controls.Conclusion Plasma RET differentiates patients with PAH from those with CTEPH, systolic or diastolic heart failure with or without pulmonary hypertension as well as healthy controls. Future studies would be of value to determine the clinical usefulness of RET as a biomarker and its link to PAH pathophysiology.Receptor tyrosine kinases have been shown to promote PAH remodelling. Plasma RET differentiates PAH from other causes of PH. RET could have the potential to be used as a future diagnostic biomarker. http://bit.ly/2LChPUS