Heresi Gustavo A, Mey Jacob T, Bartholomew John R, Haddadin Ihab S, Tonelli Adriano R, Dweik Raed A, Kirwan John P, Kalhan Satish C
Department of Pulmonary and Critical Care Medicine, Respiratory Institute, Cleveland, OH, USA.
Integrative Physiology and Molecular Medicine Laboratory, Pennington Biomedical Research Center, Baton Rouge, LA, USA.
Pulm Circ. 2020 Feb 4;10(1):2045894019890553. doi: 10.1177/2045894019890553. eCollection 2020 Jan-Mar.
We aimed to characterize the plasma metabolome of chronic thromboembolic pulmonary hypertension patients using a high-throughput unbiased omics approach. We collected fasting plasma from a peripheral vein in 33 operable chronic thromboembolic pulmonary hypertension patients, 31 healthy controls, and 21 idiopathic pulmonary arterial hypertension patients matched for age, gender, and body mass index. Metabolomic analysis was performed using an untargeted approach (Metabolon Inc. Durham, NC). Of the total of 862 metabolites identified, 362 were different in chronic thromboembolic pulmonary hypertension compared to controls: 178 were higher and 184 were lower. Compared to idiopathic pulmonary arterial hypertension, 147 metabolites were different in chronic thromboembolic pulmonary hypertension: 45 were higher and 102 were lower. The plasma metabolome allowed us to distinguish subjects with chronic thromboembolic pulmonary hypertension and healthy controls with a predictive accuracy of 89%, and chronic thromboembolic pulmonary hypertension versus idiopathic pulmonary arterial hypertension with 80% accuracy. Compared to idiopathic pulmonary arterial hypertension and healthy controls, chronic thromboembolic pulmonary hypertension patients had higher fatty acids and glycerol; while acyl cholines and lysophospholipids were lower. Compared to healthy controls, both idiopathic pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension patients had increased acyl carnitines, beta-hydroxybutyrate, amino sugars and modified amino acids and nucleosides. The plasma global metabolomic profile of chronic thromboembolic pulmonary hypertension suggests aberrant lipid metabolism characterized by increased lipolysis, fatty acid oxidation, and ketogenesis, concomitant with reduced acyl choline and phospholipid moieties. Future research should investigate the pathogenetic and therapeutic potential of modulating lipid metabolism in chronic thromboembolic pulmonary hypertension.
我们旨在采用高通量无偏倚组学方法，对慢性血栓栓塞性肺动脉高压患者的血浆代谢组进行特征分析。我们从33例可手术的慢性血栓栓塞性肺动脉高压患者、31例健康对照者以及21例年龄、性别和体重指数相匹配的特发性肺动脉高压患者的外周静脉采集空腹血浆。使用非靶向方法（北卡罗来纳州达勒姆市的Metabolon公司）进行代谢组学分析。在总共鉴定出的862种代谢物中，与对照组相比，慢性血栓栓塞性肺动脉高压中有362种不同：178种升高，184种降低。与特发性肺动脉高压相比，慢性血栓栓塞性肺动脉高压中有147种代谢物不同：45种升高，102种降低。血浆代谢组使我们能够区分慢性血栓栓塞性肺动脉高压患者和健康对照者，预测准确率为89%，区分慢性血栓栓塞性肺动脉高压与特发性肺动脉高压的准确率为80%。与特发性肺动脉高压和健康对照者相比，慢性血栓栓塞性肺动脉高压患者的脂肪酸和甘油含量更高；而酰基胆碱和溶血磷脂含量更低。与健康对照者相比，特发性肺动脉高压患者和慢性血栓栓塞性肺动脉高压患者的酰基肉碱、β-羟基丁酸、氨基糖以及修饰氨基酸和核苷均增加。慢性血栓栓塞性肺动脉高压的血浆整体代谢组学特征表明脂质代谢异常，其特征为脂解、脂肪酸氧化和生酮作用增加，同时伴有酰基胆碱和磷脂部分减少。未来的研究应调查调节慢性血栓栓塞性肺动脉高压脂质代谢的发病机制和治疗潜力。
