Background: Pulmonary Arterial Hypertension (PAH) is characterized by vasoconstriction and remodeling of distal pulmonary arteries, which result in increased Pulmonary Vascular Resistance (PVR) and right ventricular overload. In the present study, we measured plasma fluctuations of nine proteins, involved in inflammation or tyrosine kinase signaling, in PAH patients, to assess their value as biomarkers of treatment response.
Methods: Plasma vascular endothelial growth factor A and D, soluble fms-like tyrosine kinase-1 (sFlt-1), placenta growth factor, fibroblast growth factor 2, angiopoietin-1 receptor, interleukin (IL)-6 and -8 and tumor necrosis factor α were determined by multiplex immunoassays in 21 treatment-naïve PAH patients at baseline and at first and second clinical checkups.
Results: From baseline to first checkup, sFlt-1 (p<0.02) and IL-6 (p<0.005) decreased in PAH patients. sFlt-1 remained decreased (p<0.003) at the second checkup, compared to baseline. No significant changes were observed in the other measured biomarkers. Patients receiving initial combination therapy showed a more marked initial decrease (p<0.02) in plasma sFlt-1, compared to initial monotherapy. Plasma sFlt-1 changes correlated positively with changes in PVR and negatively with changes in left ventricular stroke work index (LVSWI).
Conclusion: Plasma sFlt-1 is significantly reduced after the initiation of PAH-specific treatment and its fluctuations are correlated to changes in PVR and LVSWI. Thus, plasma sFlt-1 is a new potential biomarker for evaluating treatment response in PAH