Veronika Wetzl1,2, Svenja Lena Tiede3, Lothar Faerber1,2, Norbert Weissmann3, Ralph Theo Schermuly3, Hossein Ardeschir Ghofrani3, Henning Gall4. 1. Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, Germany. 2. Novartis Pharmaceuticals, Nuremberg, Germany. 3. University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany. 4. University of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Giessen, Germany. Henning.Gall@innere.med.uni-giessen.de.
Abstract
PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are of particular interest in the remodeling processes of pulmonary hypertension. The aim of this study was to investigate MMP/TIMP ratios of selected biomarkers (MMP2, MMP9, TIMP1, TIMP4) at follow-up examination (V2) and their prognostic value in patients with idiopathic pulmonary arterial hypertension (iPAH). METHODS: Blood samples were taken from iPAH patients during right heart catheterization at diagnosis (V1, from 2003 to 2012) and first follow-up examination (V2). MMP2, MMP9, TIMP1, and TIMP4 plasma levels at V2 were determined by ELISA. Coincident with sample collection hemodynamic, laboratory, and clinical parameters were acquired. Additionally, death and clinical worsening (CW) events were listed until July 2015. RESULTS: MMP2/TIMP1 and MMP9/TIMP1 did not correlate with hemodynamic and clinical parameters. MMP2/TIMP4 showed a good correlation with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance, estimated glomerular filtration rate (eGFR), and tricuspid annular plain systolic excursion (TAPSE). MMP9/TIMP4 shows good correlation with mPAP and eGFR. MMP2/TIMP4 showed significant results in the receiver operating characteristics analysis predicting death (AUC = 0.922; p = 0.005) and CW event (AUC = 0.818; p = 0.026). Patients above the cut-off values had a significantly higher probability to die or experience CW, respectively, estimated by log-rank test (p = 0.010 for death; p = 0.032 for CW). CONCLUSIONS: MMP2/TIMP4 ratio was detected as a marker of disease severity and right ventricular function as well as a predictor for survival and time to clinical worsening and therefore might help for guidance of disease progression in iPAH patients at V2.
PURPOSE: Matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) are of particular interest in the remodeling processes of pulmonary hypertension. The aim of this study was to investigate MMP/TIMP ratios of selected biomarkers (MMP2, MMP9, TIMP1, TIMP4) at follow-up examination (V2) and their prognostic value in patients with idiopathic pulmonary arterial hypertension (iPAH). METHODS: Blood samples were taken from iPAH patients during right heart catheterization at diagnosis (V1, from 2003 to 2012) and first follow-up examination (V2). MMP2, MMP9, TIMP1, and TIMP4 plasma levels at V2 were determined by ELISA. Coincident with sample collection hemodynamic, laboratory, and clinical parameters were acquired. Additionally, death and clinical worsening (CW) events were listed until July 2015. RESULTS:MMP2/TIMP1 and MMP9/TIMP1 did not correlate with hemodynamic and clinical parameters. MMP2/TIMP4 showed a good correlation with mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance, estimated glomerular filtration rate (eGFR), and tricuspid annular plain systolic excursion (TAPSE). MMP9/TIMP4 shows good correlation with mPAP and eGFR. MMP2/TIMP4 showed significant results in the receiver operating characteristics analysis predicting death (AUC = 0.922; p = 0.005) and CW event (AUC = 0.818; p = 0.026). Patients above the cut-off values had a significantly higher probability to die or experience CW, respectively, estimated by log-rank test (p = 0.010 for death; p = 0.032 for CW). CONCLUSIONS:MMP2/TIMP4 ratio was detected as a marker of disease severity and right ventricular function as well as a predictor for survival and time to clinical worsening and therefore might help for guidance of disease progression in iPAH patientsat V2.
Authors: M Selman; V Ruiz; S Cabrera; L Segura; R Ramírez; R Barrios; A Pardo Journal: Am J Physiol Lung Cell Mol Physiol Date: 2000-09 Impact factor: 5.464
Authors: Paul R Forfia; Micah R Fisher; Stephen C Mathai; Traci Housten-Harris; Anna R Hemnes; Barry A Borlaug; Elzbieta Chamera; Mary C Corretti; Hunter C Champion; Theodore P Abraham; Reda E Girgis; Paul M Hassoun Journal: Am J Respir Crit Care Med Date: 2006-08-03 Impact factor: 21.405
Authors: Svenja L Tiede; Matthias Wassenberg; Katrin Christ; Ralph T Schermuly; Werner Seeger; Friedrich Grimminger; Hossein Ardeschir Ghofrani; Henning Gall Journal: Int J Cardiol Date: 2016-08-13 Impact factor: 4.164
Authors: Yi Ling; Martin K Johnson; David G Kiely; Robin Condliffe; Charlie A Elliot; J Simon R Gibbs; Luke S Howard; Joanna Pepke-Zaba; Karen K K Sheares; Paul A Corris; Andrew J Fisher; James L Lordan; Sean Gaine; J Gerry Coghlan; S John Wort; Michael A Gatzoulis; Andrew J Peacock Journal: Am J Respir Crit Care Med Date: 2012-07-12 Impact factor: 21.405
Authors: Griselda A Cabral-Pacheco; Idalia Garza-Veloz; Claudia Castruita-De la Rosa; Jesús M Ramirez-Acuña; Braulio A Perez-Romero; Jesús F Guerrero-Rodriguez; Nadia Martinez-Avila; Margarita L Martinez-Fierro Journal: Int J Mol Sci Date: 2020-12-20 Impact factor: 5.923