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

• Published in: International journal of molecular sciences Vol. 21; no. 6; p. 2022
• Main Authors: Bugatti, Antonella, Marsico, Stefania, Mazzuca, Pietro, Schulze, Kai, Ebensen, Thomas, Giagulli, Cinzia, Peña, Esther, Badimón, Lina, Slevin, Mark, Caruso, Arnaldo, Guzman, Carlos A, Caccuri, Francesca
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 16.03.2020; MDPI
• Subjects: Abnormalities; Acquired immune deficiency syndrome; AIDS; aids-related diseases; Animals; Anti-Retroviral Agents - therapeutic use; Antiretroviral therapy; Antithrombin; Antithrombin III - metabolism; Autophagy; Autophagy - physiology; Coagulants; Coagulation; Complex formation; Endothelial cells; Endothelial Cells - metabolism; Female; gag Gene Products, Human Immunodeficiency Virus - metabolism; HIV; HIV Antigens - metabolism; HIV Infections - complications; hiv-1; HIV-1 - physiology; Human immunodeficiency virus; Humans; Inflammation; Intravenous administration; Matrix protein; Mice; p17 matrix protein; Peptide Hydrolases - metabolism; Phagocytosis; Proteins; Secretion; Thrombin; thrombin-antithrombin complex; Von Willebrand factor; von Willebrand Factor - metabolism; HIV-1; thrombin-antithrombin complex; AIDS-related diseases; autophagy; coagulation; p17 matrix protein
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21062022

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.