title: Endothelium-derived microparticles from chronically thromboembolic pulmonary hypertensive patients facilitate endothelial angiogenesis.
abstract: BACKGROUND
  Increased circulating levels of endoglin(+) endothelial microparticles (EMPs) have been identified in several cardiovascular disorders, related to severity. Endoglin is an auxilary receptor for transforming growth factor β (TGF-β) important in the regulation of vascular structure.
  
  
  RESULTS
  We quantified the number of microparticles in plasma of six patients with chronic thromboembolic pulmonary hypertension (CTEPH) and age- and sex-matched pulmonary embolic (PE) and healthy controls and investigated the role of microparticle endoglin in the regulation of pulmonary endothelial function in vitro. Results show significantly increased levels of endoglin(+) EMPs in CTEPH plasma, compared to healthy and disease controls. Co-culture of human pulmonary endothelial cells with CTEPH microparticles increased intracellular levels of endoglin and enhanced TGF-β-induced angiogenesis and Smad1,5,8 phosphorylation in cells, without affecting BMPRII expression. In an in vitro model, we generated endothelium-derived MPs with enforced membrane localization of endoglin. Co-culture of these MPs with endothelial cells increased cellular endoglin content, improved cell survival and stimulated angiogenesis in a manner similar to the effects induced by overexpressed protein.
  
  
  CONCLUSIONS
  Increased generation of endoglin(+) EMPs in CTEPH is likely to represent a protective mechanism supporting endothelial cell survival and angiogenesis, set to counteract the effects of vascular occlusion and endothelial damage.
authors.affiliation: Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, UK.
authors.forename: Daria
authors.initials: D
authors.lastname: Belik
authors.affiliation: Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, UK.
authors.forename: Hilda
authors.initials: H
authors.lastname: Tsang
authors.affiliation: Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, UK.
authors.forename: John
authors.initials: J
authors.lastname: Wharton
authors.affiliation: National Pulmonary Hypertension Service, Imperial College Healthcare NHS Trust, London, UK.
authors.forename: Luke
authors.initials: L
authors.lastname: Howard
authors.affiliation: Centro de Investigaciones Biológicas, Consejo Superior de Investigaciones Científicas (CSIC), and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), 28040, Madrid, Spain.
authors.forename: Carmelo
authors.initials: C
authors.lastname: Bernabeu
authors.affiliation: Centre for Pharmacology and Therapeutics, Department of Medicine, Imperial College London, London, UK. b.wojciak-stothard@imperial.ac.uk.
authors.forename: Beata
authors.initials: B
authors.lastname: Wojciak-Stothard
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000473:pathology; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D006801:Humans; D006976:Hypertension, Pulmonary / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology; D011655:Pulmonary Embolism / Q000378:metabolism* / Q000473:pathology