title: Effects of C-reactive protein on human pulmonary vascular cells in chronic thromboembolic pulmonary hypertension.
abstract: Chronic thromboembolic pulmonary hypertension (CTEPH) is characterised by proximal pulmonary vascular obstruction by thrombo-fibrotic material, the origin of which has not been elucidated. Enhanced inflammation could contribute to persistent obstruction by impairing pulmonary vascular cell function in CTEPH. We investigated C-reactive protein (CRP) effects on pulmonary vascular cell function in vitro. Primary cultures of proximal pulmonary endothelial cells (ECs) and smooth muscle cells (SMCs) from CTEPH and nonthromboembolic pulmonary hypertension (PH) patients were established. Recombinant CRP effects on mitogenic activity, adhesion capacity, endothelin-1 and von Willebrand factor (vWF) secretion and intercellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule-1 expression were investigated in ECs and/or SMCs. Expression of the CRP receptor, lectin-like oxidised low-density lipoprotein receptor (LOX)-1, was evaluated in proximal pulmonary arterial tissue and cells by Western blotting and immunofluorescence. CRP increased CTEPH-SMC proliferation by 250%. CRP increased adhesion capacity, endothelin-1 and vWF secretion by CTEPH-ECs by 37%, 129% and 694%, respectively. CRP-induced adhesion of CTEPH-ECs to monocytes was mediated by ICAM-1. CRP had no effect on cells from nonthromboembolic PH patients, probably because of overexpression of LOX-1 in CTEPH. Local expression of CRP was detected in ECs and SMCs within pulmonary arterial tissue. CRP may contribute to persistent obstruction of proximal pulmonary arteries in CTEPH by promoting vascular remodelling, endothelial dysfunction and in situ thrombosis.
authors.affiliation: Respiratory Disease Dept, Katholieke Universiteit, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Wynants
authors.forename: Rozenn
authors.initials: R
authors.lastname: Quarck
authors.forename: Alicja
authors.initials: A
authors.lastname: Ronisz
authors.forename: Ernesto
authors.initials: E
authors.lastname: Alfaro-Moreno
authors.forename: Dirk
authors.initials: D
authors.lastname: Van Raemdonck
authors.forename: Bart
authors.initials: B
authors.lastname: Meyns
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
mesh_terms: D000328:Adult; D000368:Aged; D002097:C-Reactive Protein / Q000502:physiology*; D016022:Case-Control Studies; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications / Q000378:metabolism*; D007249:Inflammation / Q000150:complications / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D011651:Pulmonary Artery; D011971:Receptors, Immunologic / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D013923:Thromboembolism / Q000150:complications / Q000378:metabolism*; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: C071581:CRP protein, human; D019332:Endothelin-1; C495137:OLR1 protein, human; D011971:Receptors, Immunologic; D051127:Scavenger Receptors, Class E; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D002097:C-Reactive Protein