PMID- 24097561
OWN - NLM
STAT- MEDLINE
DCOM- 20140210
LR  - 20200930
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Linking)
VI  - 305
IP  - 12
DP  - 2013 Dec
TI  - NF-kappaB pathway is involved in CRP-induced effects on pulmonary arterial 
      endothelial cells in chronic thromboembolic pulmonary hypertension.
PG  - L934-42
LID - 10.1152/ajplung.00034.2013 [doi]
AB  - Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by 
      thrombofibrotic obstruction of proximal pulmonary arteries. The cellular and 
      molecular mechanisms underlying the pathogenesis remain incompletely understood, 
      although we recently evidenced the potential involvement of the inflammatory 
      marker C-reactive protein (CRP). We aimed to investigate the intracellular 
      mechanisms induced by CRP in proximal pulmonary arterial endothelial cells 
      (PAEC). PAEC were isolated from vascular material obtained during pulmonary 
      endarterectomy. RNA was extracted from CRP-stimulated PAEC, and first-stand cDNA 
      was generated. A RT(2) profiler PCR Array was used to evaluate the expression of 
      84 key genes related to NF-kappaB-mediated signal transduction. CRP-induced NF-kappaB 
      activation was studied. The effects of pyrrolidine-dithio-carbamate ammonium 
      (PDTC), an inhibitor of the NF-kappaB pathway, were investigated on CRP-induced 
      adhesion of monocytes to PAEC, adhesion molecule expression, endothelin-1 (ET-1), 
      interleukin-6 (IL-6), and von Willebrand factor (vWF) secretion. Compared with 
      nonstimulated PAEC, serotonin receptor 2B was downregulated by 25%, inhibitor of 
      NF-kappaB kinase subunit epsilon (IKBKE) by 30%, and toll-like receptor-4 and -6 by 
      18 and 39%, respectively, in CRP-stimulated PAEC. The transcription factor FOS 
      was threefold upregulated. CRP induced RelA/NF-kappaBp65 phosphorylation. PDTC dose 
      dependently inhibited the adhesion of monocytes to CRP-stimulated PAEC. PDTC also 
      inhibited the CRP-induced expression of ICAM-1 at the surface of PAEC. PDTC 
      impaired the secretion of ET-1 by 18% and tended to inhibit the secretion of IL-6 
      by CRP-stimulated PAEC by 46%. PDTC did not inhibit the CRP-induced secretion of 
      vWF. These results suggest an involvement of the NF-kappaB pathway in mediating 
      different effects of CRP on proximal CTEPH-PAEC.
FAU - Wynants, Marijke
AU  - Wynants M
AD  - Respiratory Division, Dept. of Clinical and Experimental Medicine - KU Leuven, 
      Onderwijs & Navorsing 1-Box 706, Herestraat 49, B-3000 Leuven, Belgium. 
      rozenn.quarck@med.kuleuven.be.
FAU - Vengethasamy, Leanda
AU  - Vengethasamy L
FAU - Ronisz, Alicja
AU  - Ronisz A
FAU - Meyns, Bart
AU  - Meyns B
FAU - Delcroix, Marion
AU  - Delcroix M
FAU - Quarck, Rozenn
AU  - Quarck R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131004
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (NF-kappa B)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - C-Reactive Protein/*metabolism
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Endothelial Cells/*metabolism
MH  - Endothelium, Vascular/cytology
MH  - Female
MH  - Humans
MH  - Hypertension, Pulmonary/etiology/*metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Male
MH  - Middle Aged
MH  - NF-kappa B/*metabolism
MH  - Pulmonary Artery/cytology/*metabolism
MH  - Pulmonary Embolism/complications/*metabolism
MH  - Signal Transduction/*physiology
OTO - NOTNLM
OT  - C-reactive protein
OT  - NF-kappaB
OT  - chronic thromboembolic pulmonary hypertension
OT  - endothelial cells
EDAT- 2013/10/08 06:00
MHDA- 2014/02/11 06:00
CRDT- 2013/10/08 06:00
PHST- 2013/10/08 06:00 [entrez]
PHST- 2013/10/08 06:00 [pubmed]
PHST- 2014/02/11 06:00 [medline]
AID - ajplung.00034.2013 [pii]
AID - 10.1152/ajplung.00034.2013 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2013 Dec;305(12):L934-42. doi: 
      10.1152/ajplung.00034.2013. Epub 2013 Oct 4.