Diagnostic and prognostic significance of serum angiopoietin-1 and -2 concentrations in patients with pulmonary hypertension

Abstract

Several biomarkers for detecting pulmonary hypertension (PH) have been reported. However, these biomarkers are deemed insufficient to detect PH in its early stages. We evaluated the utility of serum angiopoietin (ANGP), a glycoprotein related to angiogenesis, as a diagnostic and prognostic biomarker of PH. Patients with PH who underwent right-heart catheterization, were retrospectively studied. Serum concentrations of ANGP-1 and ANGP-2 were measured using an enzyme-linked immunosorbent assay in patients with PH (n = 32), those with idiopathic pulmonary fibrosis (IPF) without PH (as a disease control, n = 75), and age-matched healthy controls (HC, n = 60). Nineteen patients (59.4%) with PH had World Health Organization group 3 PH. Serum ANGP-2 concentration, but not ANGP-1, in patients with PH was significantly higher compared with that in HC (p = 0.025) and in patients with IPF without PH (p = 0.008). Serum ANGP-2 concentration in patients with PH positively and significantly correlated with N-terminal pro-B-type natriuretic peptide (r = 0.769, p < 0.001), right ventricular diameter on echocardiography (r = 0.565, p = 0.035), and mean pulmonary arterial pressure (r = 0.449, p = 0.032) and pulmonary vascular resistance (r = 0.451, p = 0.031) on right-heart catheterization. ANGP-1 and ANGP-2 were expressed on lung vascular endothelial cells, as shown by immunohistochemistry. Patients with PH with higher ANGP-2 concentration (≥ 2.48 ng/mL) had significantly worse survival (p = 0.022). Higher ANGP-2 concentration was a significant worse prognostic factor (hazard ratio = 6.063, p = 0.037), while serum ANGP-1 concentration was not. In conclusion, serum ANGP-2 may be a useful diagnostic and prognostic biomarker in patients with PH, especially in patients with group 3 PH.

Serum angiopoietin-1 concentration does not distinguish patients with ischaemic stroke from those presenting to hospital with ischaemic stroke mimics

“…This was necessary as platelet-free plasma required by available assays could not be obtained from the current cohort. Nonetheless, previous studies have reported significant differences in serum angpt-1 concentrations between comparator groups demonstrating that serum is a suitable medium for investigating angpt-1 expression [ 21 – 23 ].…”

Role of heparanase in pulmonary hypertension

“…For instance, elevated levels of VEGF have been associated with vascular smooth muscle cell proliferation in a mouse model of hypoxic PH ( Liu et al, 2018 ). High concentrations of Ang-2 and bFGF have been identified as significant poor prognostic factors in PH ( Seyfarth et al, 2015 ; Enomoto et al, 2021 ). It can be seen that there is a close relationship between HPA and pulmonary artery endothelial cells.…”

Biomarkers in Pulmonary Arterial Hypertension

“…Kumpers et al showed that ANG2 was statistically significantly correlated with CI, PVR, and mvSatO 2 , confirming its involvement in the pathogenesis of IPAH [ 88 ]. However, additional information has emerged more recently, suggesting that ANG2 is not associated with treatment response in patients with IPAH [ 89 ], although it may be used as a diagnostic and prognostic marker in Group 3 patients with PH.…”