title: The role of circulating thrombospondin-1 in patients with precapillary pulmonary hypertension.
abstract: The vasoconstrictive protein TSP-1 is released from endothelial cells upon increased shear stress and hypoxia. Both conditions are prevalent in pulmonary hypertension (PH). TSP-1 damages the local microcirculation by disrupting pathways, which are essential for specific medical therapeutics. Furthermore, TSP-1 induces excessive fibrosis and smooth muscle proliferation - a common finding in advanced PH - via TGF-ß and might promote disease progression. The prognostic impact of circulating TSP-1, influence on hemodynamic parameters and interaction with other biomarkers in patients with PH is incompletely understood. This study examines prospectively circulating TSP-1 in association with hemodynamic parameters, clinical variables and mortality.
  
  
  
  Circulating TSP-1 was measured prospectively in 93 patients with precapillary PH undergoing right heart catheterization and in 19 subjects without PH. TSP-1 levels were determined by ELISA and examined in the context of hemodynamic variables. For evaluation of survival, patients were monitored for adverse events on a 3-monthly basis and contacted at the end of the study after 5 years. In addition, levels of big-endothelin and humoral cofactors of TSP-1 release were measured.
  
  
  
  Patients with PH had significantly increased TSP-1 levels compared to controls without PH (1114 ± 136 ng/mL vs. 82.1 ± 15.8 ng/mL, p < 0.05). Levels were correlated with mean pulmonary artery pressure (PAPm, r = -0.58, p < 0.001) and pulmonary vascular resistance (PVR, r = 0.33, p = 0.002). Survivors had lower TSP-levels as non-survivors and all cause mortality associated with TSP-1 plasma levels above 2051 ng/mL (p = 0.0002, HR 1.49).
  
  
  
  High plasma levels of TSP-1 are associated with increased PAPm, increased PVR and decreased survival. Due to its interaction with therapeutic pathways, studies are warranted to clarify the impact of TSP-1 on of specific medications for PH.
authors.affiliation: Department of Internal Medicine V Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University, Kirrberger Strasse, D-66424, Homburg/Saar, Germany. ralfkaiser@gmx.net.
authors.forename: Ralf
authors.identifier: 0000-0003-1458-162X
authors.initials: R
authors.lastname: Kaiser
authors.affiliation: Department of Pulmonology, Hôpitaux Robert Schuman - Zithaklinik, 38-40 Rue Sainte Zithe, L-2763, Luxembourg, Luxembourg.
authors.forename: Christian
authors.initials: C
authors.lastname: Frantz
authors.affiliation: Department of Internal Medicine V Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University, Kirrberger Strasse, D-66424, Homburg/Saar, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Bals
authors.affiliation: Department of Internal Medicine V Pulmonology, Allergology, Respiratory Intensive Care Medicine, Saarland University, Kirrberger Strasse, D-66424, Homburg/Saar, Germany.
authors.forename: Heinrike
authors.initials: H
authors.lastname: Wilkens
mesh_terms: D000328:Adult; D000368:Aged; D062186:Arterial Pressure; D015415:Biomarkers / Q000097:blood; D006328:Cardiac Catheterization; D016022:Case-Control Studies; D019332:Endothelin-1 / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000097:blood* / Q000175:diagnosis / Q000401:mortality / Q000503:physiopathology; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D011651:Pulmonary Artery / Q000503:physiopathology; D012307:Risk Factors; D019700:Thrombospondin 1 / Q000097:blood*; D013997:Time Factors; D015854:Up-Regulation; D014655:Vascular Resistance
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D019700:Thrombospondin 1; C000611726:thrombospondin-1, human