Circulating regulators of the wingless pathway in precapillary pulmonary hypertension

Background and objective Dysregulated Wnt signalling has been implicated in pulmonary hypertension (PH). We hypothesized that plasma levels of secreted proteins would be increased patients with precapillary PH, correlate indices vascular resistance cardiac function give information on long-term prognosis. Methods measured the ligand Wnt5a antagonists Dickkopf (DKK) DKK1, DKK3, frizzled-related protein 3 (sFRP3), inhibitory factor-1 (WIF1) sclerostin (SOST) 106 PH 40 healthy controls. A second sample was obtained after a median 4 months (n = 52). During 90 follow-up, 67 died. Results Our main findings were (i) Precapillary is characterized by enhanced systemic activity as reflected elevated irrespective diagnostic subgroups. (ii) WIF1 particular correlated dysfunction. (iii) High Wnt5a, sFRP3, DKK3 associated poor prognosis age- sex-adjusted analysis (hazard ratios per log/SD change ~1.4) for further adjustment right arterial pressure, oxygen saturation, index, N-terminal pro B-type natriuretic peptide peak uptake (VO2). Finally, an elevation during follow-up independently Conclusion data indicate pathways could pathogenesis some Wnt-related molecules (i.e., DKK3) should investigated these patients.