PMID- 28516393
OWN - NLM
STAT- MEDLINE
DCOM- 20180507
LR  - 20231213
IS  - 1432-1750 (Electronic)
IS  - 0341-2040 (Linking)
VI  - 195
IP  - 4
DP  - 2017 Aug
TI  - Plasma MMP2/TIMP4 Ratio at Follow-up Assessment Predicts Disease Progression of 
      Idiopathic Pulmonary Arterial Hypertension.
PG  - 489-496
LID - 10.1007/s00408-017-0014-5 [doi]
AB  - 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.
FAU - Wetzl, Veronika
AU  - Wetzl V
AD  - Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, 
      Germany.
AD  - Novartis Pharmaceuticals, Nuremberg, Germany.
FAU - Tiede, Svenja Lena
AU  - Tiede SL
AD  - University of Giessen and Marburg Lung Center (UGMLC), Member of the German 
      Center for Lung Research (DZL), Giessen, Germany.
FAU - Faerber, Lothar
AU  - Faerber L
AD  - Department of Pharmacology and Toxicology, University of Regensburg, Regensburg, 
      Germany.
AD  - Novartis Pharmaceuticals, Nuremberg, Germany.
FAU - Weissmann, Norbert
AU  - Weissmann N
AD  - University of Giessen and Marburg Lung Center (UGMLC), Member of the German 
      Center for Lung Research (DZL), Giessen, Germany.
FAU - Schermuly, Ralph Theo
AU  - Schermuly RT
AD  - University of Giessen and Marburg Lung Center (UGMLC), Member of the German 
      Center for Lung Research (DZL), Giessen, Germany.
FAU - Ghofrani, Hossein Ardeschir
AU  - Ghofrani HA
AD  - University of Giessen and Marburg Lung Center (UGMLC), Member of the German 
      Center for Lung Research (DZL), Giessen, Germany.
FAU - Gall, Henning
AU  - Gall H
AD  - 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.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170517
PL  - United States
TA  - Lung
JT  - Lung
JID - 7701875
RN  - 0 (Biomarkers)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - EC 3.4.24.24 (MMP2 protein, human)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Aged
MH  - Area Under Curve
MH  - Biomarkers/blood
MH  - Cardiac Catheterization
MH  - Disease Progression
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Familial Primary Pulmonary 
      Hypertension/blood/*diagnosis/mortality/physiopathology
MH  - Female
MH  - Hemodynamics
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Male
MH  - Matrix Metalloproteinase 2/*blood
MH  - Middle Aged
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - ROC Curve
MH  - Retrospective Studies
MH  - Risk Factors
MH  - Severity of Illness Index
MH  - Time Factors
MH  - Tissue Inhibitor of Metalloproteinases/*blood
MH  - Ventricular Function, Right
MH  - Tissue Inhibitor of Metalloproteinase-4
OTO - NOTNLM
OT  - Heart failure [C14.280.434]
OT  - Hypertension, pulmonary [C08.381.423]
OT  - Matrix metalloproteinases [D08.811.277.656.675.374.525]
OT  - Prognosis [E01.789]
OT  - Survival analysis [E05.318.740.998]
EDAT- 2017/05/19 06:00
MHDA- 2018/05/08 06:00
CRDT- 2017/05/19 06:00
PHST- 2017/01/27 00:00 [received]
PHST- 2017/05/08 00:00 [accepted]
PHST- 2017/05/19 06:00 [pubmed]
PHST- 2018/05/08 06:00 [medline]
PHST- 2017/05/19 06:00 [entrez]
AID - 10.1007/s00408-017-0014-5 [pii]
AID - 10.1007/s00408-017-0014-5 [doi]
PST - ppublish
SO  - Lung. 2017 Aug;195(4):489-496. doi: 10.1007/s00408-017-0014-5. Epub 2017 May 17.