Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension

Cytokines can modulate vascular remodelling and the adaptation of the right ventricle in pre-capillary pulmonary hypertension (PH). However, detailed data on the circulating levels of cytokines in patients are limited. We measured blood cytokine concentration in 39 treatment-naive patients (pulmonary arterial hypertension: N = 16, chronic thromboembolic PH: N = 15, PH due to lung disease: N = 8) and 12 control subjects using enzyme-linked immunoassays. Apelin concentration >1,261 ng/mL identified patients with PH (66% sensitivity and 82% specificity), and in patients it was related to systolic pulmonary arterial pressure (PAP) (r = 0.33, P 5 0.04), right atrial pressure (r = 0.38, P = 0.02), cardiac index (r = (+/-)0.34, P = 0.04), and right ventricular stroke work index (r 5 (+/-)0.47, P 5 0.003). IL22RA2 concentration correlated with mean PAP (r = (+/-)0.32, P 5 0.04) and serum N-terminal pro B-type natriuretic peptide level (r 5 (+/-)0.42, P 5 0.01). VEGF concentration increased in patients upon clinical improvement (N = 16, P = 0.02). Circulating apelin is a novel biomarker of pre-capillary PH. Apelin and IL22RA2 levels are related to right ventricular function upon diagnosis of PH.