Plasma metabolomic profile in chronic thromboembolic pulmonaryhypertension

摘要

We aimed to characterize the plasma metabolome of chronic thromboembolicpulmonary hypertension patients using a high-throughput unbiased omics approach.We collected fasting plasma from a peripheral vein in 33 operable chronicthromboembolic pulmonary hypertension patients, 31 healthy controls, and 21idiopathic pulmonary arterial hypertension patients matched for age, gender, andbody mass index. Metabolomic analysis was performed using an untargeted approach(Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362were different in chronic thromboembolic pulmonary hypertension compared tocontrols: 178 were higher and 184 were lower. Compared to idiopathic pulmonaryarterial hypertension, 147 metabolites were different in chronic thromboembolicpulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolomeallowed us to distinguish subjects with chronic thromboembolic pulmonaryhypertension and healthy controls with a predictive accuracy of 89%, and chronicthromboembolic pulmonary hypertension versus idiopathic pulmonary arterialhypertension with 80% accuracy. Compared to idiopathic pulmonary arterialhypertension and healthy controls, chronic thromboembolic pulmonary hypertensionpatients had higher fatty acids and glycerol; while acyl cholines andlysophospholipids were lower. Compared to healthy controls, both idiopathicpulmonary arterial hypertension and chronic thromboembolic pulmonaryhypertension patients had increased acyl carnitines, beta-hydroxybutyrate, aminosugars and modified amino acids and nucleosides. The plasma global metabolomicprofile of chronic thromboembolic pulmonary hypertension suggests aberrant lipidmetabolism characterized by increased lipolysis, fatty acid oxidation, andketogenesis, concomitant with reduced acyl choline and phospholipid moieties.Future research should investigate the pathogenetic and therapeutic potential ofmodulating lipid metabolism in chronic thromboembolic pulmonaryhypertension.