title: Contribution of inflammation and impaired angiogenesis to the pathobiology of chronic thromboembolic pulmonary hypertension.
abstract: Deficient angiogenesis and systemic inflammation could be involved in the pathophysiology of chronic thromboembolic pulmonary hypertension (CTEPH). We aimed to characterise the histopathology of pulmonary vascular lesions from 52 CTEPH patients who underwent a pulmonary endarterectomy (PEA) and investigate a potential link between clinical, biological and morphometric parameters.Collagen, elastin, fibrin, lipid, endothelial, smooth muscle and inflammatory cell content was investigated using immunohistochemistry. Qualitative changes were evaluated using severity scores. Circulating levels of inflammatory mediators were measured using ELISA.Neointima, thrombotic, recanalised and atherosclerotic lesions were found. Accumulation of macrophages, T-lymphocytes and neutrophils was found mainly in atherosclerotic and thrombotic lesions. Angiogenesis was observed in all kinds of lesions; low-scored angiogenesis predicted adverse outcome, including persistent pulmonary hypertension post-PEA, start of medical therapy and poor survival. C-reactive protein (CRP), interleukin-10, monocyte chemotactic protein-1, macrophage inflammatory protein-1α and matrix metalloproteinase (MMP)-9 were significantly elevated in CTEPH patients. Plasma CRP and MMP-9 levels correlated with neutrophil and macrophage accumulation, respectively.Enhanced systemic inflammation parallels local inflammatory cell infiltration in major pulmonary arteries at advanced stages of CTEPH. Impaired neovascularisation is associated with poor survival, start of medical treatment and persistent pulmonary hypertension post-PEA. These findings suggest that inflammation and impaired angiogenesis could contribute to the progression of the disease.
authors.affiliation: Respiratory Division, Dept of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium rozenn.quarck@med.kuleuven.be.
authors.forename: Rozenn
authors.initials: R
authors.lastname: Quarck
authors.affiliation: Respiratory Division, Dept of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Wynants
authors.affiliation: Translational Cell & Tissue Research, University of Leuven, Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: Verbeken
authors.affiliation: Cardiac Surgery Dept, University Hospitals Leuven, Leuven, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Meyns
authors.affiliation: Respiratory Division, University Hospitals and Dept of Clinical and Experimental Medicine, University of Leuven, Leuven, Belgium.
authors.forename: Marion
authors.initials: M
authors.lastname: Delcroix
mesh_terms: D015415:Biomarkers; D002097:C-Reactive Protein / Q000032:analysis; D018932:Chemokine CCL2 / Q000097:blood; D054405:Chemokine CCL3 / Q000097:blood; D002908:Chronic Disease; D018450:Disease Progression; D004691:Endarterectomy; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000473:pathology* / Q000601:surgery; D007249:Inflammation / Q000150:complications*; D016753:Interleukin-10 / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D011651:Pulmonary Artery / Q000473:pathology*; D011655:Pulmonary Embolism / Q000150:complications*
chemical_list: D015415:Biomarkers; C111835:CCL2 protein, human; C515429:CCL3 protein, human; D018932:Chemokine CCL2; D054405:Chemokine CCL3; C508609:IL10 protein, human; D016753:Interleukin-10; D002097:C-Reactive Protein; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9