Open AccessPlasma 12‐ and 15‐Hydroxyeicosanoids are Predictors of Survival in Pulmonary Arterial Hypertension
Author(s) -
AlNaamani Nadine,
Sagliani Kristen D.,
Dolnikowski Gregory G.,
Warburton Rod R.,
Toksoz Deniz,
Kayyali Usamah,
Hill Nicholas S.,
Fanburg Barry L.,
Roberts Kari E.,
Preston Ioana R.
Publication year - 2016
Publication title -
pulmonary circulation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.791
H-Index - 40
ISSN - 2045-8940
DOI - 10.1086/686311
Subject(s) - medicine , prostacyclin , hazard ratio , hypoxia (environmental) , thromboxane , pulmonary hypertension , gastroenterology , confidence interval , eicosanoid , lung , cohort , endocrinology , cardiology , arachidonic acid , platelet , biochemistry , chemistry , organic chemistry , oxygen , enzyme
This study aimed to characterize alterations in select eicosanoids in experimental and human pulmonary arterial hypertension (PAH) and to assess their potential utility as predictors of outcome. Using liquid chromatography–mass spectrometry, we performed targeted lipidomic analyses of the lungs and right ventricles (RVs) of chronically hypoxic rats and plasma of consecutive PAH patients and healthy controls. In rat lungs, chronic hypoxia was associated with significantly decreased lung prostacyclin (PGI 2 )/thromboxane B 2 (TXB 2 ) ratio and elevated lung 8‐hydroxyeicosanoid (HETE) acid concentrations. RV eicosanoids did not exhibit any changes with chronic hypoxia. PAH treatment–naïve patients had significantly increased plasma concentrations of TXB 2 and 5‐, 8‐, 12‐, and 15‐HETE. The PGI 2 /TXB 2 ratio was lower in PAH patients than in controls, especially in the treatmentnaïve cohort (median: 2.1, 0.3, and 1.3 in controls, treatmentnaïve, and treated patients, respectively, P = 0.001). Survival was significantly worse in PAH patients with 12‐HETE high (≥57 pg/mL) and 15‐HETE high (≥256 pg/mL) in unadjusted and adjusted analyses (hazard ratio [HR]: 2.8 [95% confidence interval (CI): 1.1–7.3], P = 0.04 and HR: 4.3 [95% CI: 1.6–11.8], P = 0.004, respectively; adjustment was performed with the REVEAL [Registry to Evaluate Early and Long‐Term PAH Disease Management] risk score). We demonstrate significant alterations in eicosanoid pathways in experimental and human PAH. We found that 12‐ and 15‐HETE were independent predictors of survival in human PAH, even after adjusting for the REVEAL score, suggesting their potential role as novel biomarkers.