Role of autophagy in von willebrand factor secretion by endothelial cells and in the in vivo thrombin-antithrombin complex formation promoted by the hiv-1 matrix protein p17
Bugatti, A. (University of Brescia Medical School)
Marsico, S. (University of Calabria)
Mazzuca, P. (University of Brescia Medical School)
Schulze, K. (Helmholtz Center for Infection Research (HZI))
Ebensen, T. (Helmholtz Center for Infection Research (HZI))
Giagulli, C. (University of Brescia Medical School)
Peña, Esther (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Slevin, M. (Manchester Metropolitan University)
Caruso, A. (University of Brescia Medical School)
Guzman, C.A. (Helmholtz Center for Infection Research (HZI))
Caccuri, F. (University of Brescia Medical School)
Universitat Autònoma de Barcelona

Fecha:	2020
Resumen:	Although the advent of combined antiretroviral therapy has substantially improved the survival of HIV-1-infected individuals, non-AIDS-related diseases are becoming increasingly prevalent in HIV-1-infected patients. Persistent abnormalities in coagulation appear to contribute to excess risk for a broad spectrum of non-AIDS defining complications. Alterations in coagulation biology in the context of HIV infection seem to be largely a consequence of a chronically inflammatory microenvironment leading to endothelial cell (EC) dysfunction. A possible direct role of HIV-1 proteins in sustaining EC dysfunction has been postulated but not yet investigated. The HIV-1 matrix protein p17 (p17) is secreted from HIV-1-infected cells and is known to sustain inflammatory processes by activating ECs. The aim of this study was to investigate the possibility that p17-driven stimulation of human ECs is associated with increased production of critical coagulation factors. Here we show the involvement of autophagy in the p17-induced accumulation and secretion of von Willebrand factor (vWF) by ECs. In vivo experiments confirmed the capability of p17 to exert a potent pro-coagulant activity soon after its intravenous administration.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	AIDS-related disease ; Autophagy ; Coagulation ; HIV-1 ; P17 matrix protein ; Thrombin-antithrombin complex
Publicado en:	International journal of molecular sciences, Vol. 21 Núm. 6 (february 2020) , p. 2022, ISSN 1422-0067

DOI: 10.3390/ijms21062022
PMID: 32188077

16 p, 2.9 MB

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