PMID- 31156142
OWN - NLM
STAT- MEDLINE
DCOM- 20200330
LR  - 20200330
IS  - 1875-8622 (Electronic)
IS  - 1386-0291 (Linking)
VI  - 73
IP  - 4
DP  - 2019
TI  - Cellular inflammation in pulmonary hypertension: Detailed analysis of lung and 
      right ventricular tissue, circulating immune cells and effects of a dual 
      endothelin receptor antagonist.
PG  - 497-522
LID - 10.3233/CH-180529 [doi]
AB  - Growing evidence suggests that inflammation is crucially involved in the 
      pathogenesis of pulmonary hypertension (PH) and consecutive right heart failure. 
      The present study analyzed the inflammatory response in lung and right ventricle 
      in a rat model of PH and evaluated the effects of the dual endothelin receptor 
      antagonist (ERA) Macitentan. PH was induced by monocrotalin (60 mg/kg body weight 
      s.c.) in Sprague-Dawley rats (PH, n = 10) and compared to healthy controls (CON, 
      n = 10) as well as monocrotalin-induced, macitentan-treated rats (THER, n = 10). 
      Detection of Dendritic cells (DCs), regulatory T cells (Tregs) and others as well 
      as RT-PCR based inflammatory gene expression analysis were performed. Circulating 
      DCs and Tregs were quantified by flow cytometry in the rat model and in PH 
      patients (n = 70) compared to controls (n = 52). Inflammatory cells were 
      increased in lung and right ventricular tissue, whereas DCs and Tregs were 
      decreased in blood. Expression of 17 genes in the lung and 20 genes in the right 
      ventricle were relevantly (>2.0 fold) regulated in the PH group. These effects 
      were, at least in part, attenuated in response to Macitentan treatment. In humans 
      as well as rats, immune cells showed significant correlations to clinical, 
      echocardiographic, and haemodynamic parameters. PH is accompanied by a distinct 
      inflammatory response in lung and right but not left ventricular tissue 
      attenuated by Macitentan. Correlations of circulating DCs as well as tissue 
      resident immune cells with parameters reflecting right ventricular function raise 
      the idea of both, promising biomarkers and novel treatment strategies.
FAU - Rohm, Ilonka
AU  - Rohm I
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Grun, Katja
AU  - Grun K
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Muller, Linda Marleen
AU  - Muller LM
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Baz, Laura
AU  - Baz L
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Forster, Martin
AU  - Forster M
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Schrepper, Andrea
AU  - Schrepper A
AD  - Department of Cardiothoracic Surgery, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Kretzschmar, Daniel
AU  - Kretzschmar D
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Pistulli, Rudin
AU  - Pistulli R
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Yilmaz, Atilla
AU  - Yilmaz A
AD  - Department of Internal Medicine II, Division of Cardiology, Elisabeth Klinikum 
      Schmalkalden, Schmalkalden, Germany.
FAU - Bauer, Reinhard
AU  - Bauer R
AD  - Institute of Molecular Cell Biology, Center for Molecular Biomedicine, Jena 
      University Hospital, Jena, Germany.
FAU - Jung, Christian
AU  - Jung C
AD  - Department of Internal Medicine, Division of Cardiology, University Hospital 
      Dusseldorf, Heinrich Heine University, Dusseldorf, Germany.
FAU - Berndt, Alexander
AU  - Berndt A
AD  - Institute of Pathology, University Hospital Jena, Friedrich-Schiller-University, 
      Jena, Germany.
FAU - Schulze, P Christian
AU  - Schulze PC
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
FAU - Franz, Marcus
AU  - Franz M
AD  - Department of Internal Medicine I, Division of Cardiology, Angiology, Pneumology, 
      and Intensive Medical Care, University Hospital Jena, 
      Friedrich-Schiller-University, Jena, Germany.
LA  - eng
PT  - Journal Article
PL  - Netherlands
TA  - Clin Hemorheol Microcirc
JT  - Clinical hemorheology and microcirculation
JID - 9709206
RN  - 0 (Endothelin A Receptor Antagonists)
SB  - IM
MH  - Animals
MH  - Disease Models, Animal
MH  - Endothelin A Receptor Antagonists/pharmacology/*therapeutic use
MH  - Humans
MH  - Hypertension, Pulmonary/*drug therapy/*physiopathology
MH  - Lung/*pathology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
OTO - NOTNLM
OT  - biomarker
OT  - dual endothelin receptor antagonist
OT  - inflammation
OT  - pulmonary hypertension
OT  - right heart failure
EDAT- 2019/06/04 06:00
MHDA- 2020/03/31 06:00
CRDT- 2019/06/04 06:00
PHST- 2019/06/04 06:00 [pubmed]
PHST- 2020/03/31 06:00 [medline]
PHST- 2019/06/04 06:00 [entrez]
AID - CH180529 [pii]
AID - 10.3233/CH-180529 [doi]
PST - ppublish
SO  - Clin Hemorheol Microcirc. 2019;73(4):497-522. doi: 10.3233/CH-180529.