Endothelium-derived microparticles from chronically thromboembolic pulmonary hypertensive patients facilitate endothelial angiogenesis
Autor: | Hilda Tsang, Beata Wojciak-Stothard, Carmelo Bernabeu, Luke Howard, John Wharton, Daria Belik |
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Přispěvatelé: | Ministerio de Economía y Competitividad (España) |
Jazyk: | angličtina |
Předmět: |
Male
0301 basic medicine Angiogenesis Endocrinology Diabetes and Metabolism Clinical Biochemistry 030204 cardiovascular system & hematology Neovascularization 0302 clinical medicine Cell-Derived Microparticles hemic and lymphatic diseases Pharmacology (medical) Aged 80 and over Neovascularization Pathologic Endoglin General Medicine 11 Medical And Health Sciences Middle Aged 3. Good health Endothelial stem cell medicine.anatomical_structure Female medicine.symptom Adult Biochemistry & Molecular Biology Endothelium Hypertension Pulmonary Microparticles Pulmonary hypertension 03 medical and health sciences medicine otorhinolaryngologic diseases Humans Molecular Biology Aged Biochemistry medical 08 Information And Computing Sciences business.industry Research Biochemistry (medical) Cell Biology 06 Biological Sciences medicine.disease 030104 developmental biology Cancer research Endothelium Vascular Pulmonary Embolism business Transforming growth factor |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Journal of Biomedical Science |
ISSN: | 1423-0127 |
DOI: | 10.1186/s12929-016-0224-9 |
Popis: | 11 p.-4 fig.-1 tab. 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. This research was supported by a project grant (PG 11/13/28765) from the British Heart Foundation and by grants from Ministerio de Economia y Competitividad of Spain (SAF2013-43421-R to CB) |
Databáze: | OpenAIRE |
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