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
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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