Int J Med Sci 2019; 16(2):276-284. doi:10.7150/ijms.28110

Research Paper

Von Willebrand Factor Adhesive Activity and ADAMTS13 Protease Activity in HIV-1-Infected Men

Susan M. Graham1,2,3, Junmei Chen4, Jennie Le4, Minhua Ling4, Dominic W. Chung4, W. Conrad Liles1,2,5,6, José A. López1,4,7,8✉

1. Department of Medicine, University of Washington, Seattle, WA USA
2. Department of Global Health, University of Washington, Seattle, WA USA
3. Department of Epidemiology, University of Washington, Seattle, WA USA
4. Bloodworks Research Institute, Seattle, WA, USA
5. Department of Pathology, University of Washington, Seattle, WA USA
6. Department of Pharmacology, University of Washington, Seattle, WA, USA
7. Department of Biochemistry, University of Washington, Seattle, WA USA
8. Department of Mechanical Engineering, University of Washington, Seattle, WA, USA

Abstract

Background: Endothelial activation caused by HIV-1 infection leads to release of von Willebrand factor (VWF), which enters the circulation or attaches to vessel walls and self-assembles into strings and fibers, enabling platelet adhesion; this adhesive activity is regulated by the VWF-cleaving protease ADAMTS13. Our objective was to assess VWF adhesive activity and ADAMTS13 protease activity in HIV-1 infection.

Methods: We measured levels of VWF antigen, VWF activation factor (a measure of adhesive activity), ADAMTS13 antigen, ADAMTS13 activity, and apolipoprotein A1 (which interferes with VWF self-association) in serum samples from HIV-1-infected men whose infections were acute (n=10), chronic untreated (n=10), or chronic treated (n=10), compared to uninfected controls (n=10). Means across groups were compared using analysis of variance with contrasts, and Pearson correlations were calculated.

Results: Plasma viral load was positively correlated with VWF adhesive activity, which was elevated in acute relative to chronic treated HIV-1 infection. ADAMTS13 antigen and activity were both positively correlated with plasma viral load, and ADAMTS13 activity was significantly higher in men with acute HIV infection than in uninfected controls, and in both acute and chronic untreated HIV infection relative to chronic treated infection.

Conclusion: These findings suggest that even in the setting of increased ADAMTS13 protease activity, VWF in HIV-1 infection is hyperadhesive, which may favor development of microvascular and arterial thromboses and thereby contribute to increased cardiovascular risk in HIV-1-infected individuals.

Keywords: HIV-1, von Willebrand factor, ADAMTS13 protein, apolipoprotein A1, thrombosis

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How to cite this article:
Graham SM, Chen J, Le J, Ling M, Chung DW, Liles WC, López JA. Von Willebrand Factor Adhesive Activity and ADAMTS13 Protease Activity in HIV-1-Infected Men. Int J Med Sci 2019; 16(2):276-284. doi:10.7150/ijms.28110. Available from http://www.medsci.org/v16p0276.htm