title: Serum levels of tumor necrosis factor-related apoptosis-inducing ligand correlate with the severity of pulmonary hypertension.
abstract: Pulmonary hypertension (PH) is a rapidly progressive disease that eventually leads to right heart failure and death. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its receptors (TRAIL-Rs) play an important role in the survival, migration, and proliferation of vascular smooth muscle cells. However, the association between serum TRAIL levels and PH is unknown. In this study, we assayed the serum soluble TRAIL (sTRAIL) levels in 78 patients with PH and 80 controls. The sTRAIL concentrations were elevated in the PH patients compared with the controls (138.76 ± 6.60 pg/mL vs. 80.14 ± 3.38 pg/mL, p < 0.0001). The presence of sTRAIL levels of >103 pg/mL could discriminate PH patients from healthy individuals, with a sensitivity of 75.6% and specificity of 81.2%. Moreover, elevated sTRAIL concentrations were associated with eventual pathological complications; this is consistent with the finding that sTRAIL levels decreased in patients who responded to treatment. In a hypoxia-induced PH mouse model, sTRAIL levels were significantly higher compared with those in normoxia mice, and clearly decreased when the mice were treated with treprostinil. The sTRAIL levels were positively correlated with right ventricular systolic pressure and the index of right ventricular hypertrophy. In conclusion, serum sTRAIL could be a biomarker for diagnosis and effective therapy for PH patients.
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Huan
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Erli
authors.initials: E
authors.lastname: Yang
authors.affiliation: Department of Obstetrics and Genecology, Armed Police Hospital of Shanghai, Shanghai 201103, China.
authors.forename: Xiaolan
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Caojian
authors.initials: C
authors.lastname: Zuo
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Yuhu
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China.
authors.forename: Daile
authors.initials: D
authors.lastname: Jia
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China; Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Food Safety Research, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cardiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China. Electronic address: lvankangrj@163.com.
authors.forename: Ankang
authors.initials: A
authors.lastname: Lv
mesh_terms: D000818:Animals; D016022:Case-Control Studies; D004195:Disease Models, Animal; D011464:Epoprostenol / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D011446:Prospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000097:blood*
chemical_list: D053221:TNF-Related Apoptosis-Inducing Ligand; D011464:Epoprostenol; C427248:treprostinil
keywords: Mouse model; Pulmonary hypertension; Tumor necrosis factor-related apoptosis-inducing ligand