Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus
Plasma vascular endothelial growth factor (VEGF) coreceptor neuropilin-1 (NRP-1) had the largest association with coronary plaque in the Randomized Trial to Prevent Vascular Events in HIV (REPRIEVE) proteomics analysis. With little known about NRP-1 in people with human immunodeficiency virus (PWH), we explored its relation to other proteins in REPRIEVE and validated our findings through a Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) case-cohort study by assessing its relation to host factors and incident cardiovascular disease and cancer. Within REPRIEVE, NRP-1 was associated with proteins involved in angiogenesis, signal transduction, immunoregulation, and cell migration/adhesion. Within CNICS, NRP-1 was associated with key host factors, including older age and male sex. NRP-1 was associated with an increased hazard of multiple cancers but a decreased prostate cancer risk. Finally, NRP-1 was most strongly associated with mortality and type 2 myocardial infarction. These data suggest that NRP-1 is part of a clinically relevant immunoregulatory pathway related to multiple comorbidities in PWH. <strong>Clinical Trials Registration</strong>. NCT02344290.
Authors
- Márton Kolossváry (ORCID: https://orcid.org/0000-0002-5570-991X)
- Markella V. Zanni (ORCID: https://orcid.org/0000-0002-4711-3956)
- Fay Chan
- Heather J. Ribaudo (ORCID: https://orcid.org/0000-0002-0394-3990)
- Carl J. Fichtenbaum (ORCID: https://orcid.org/0000-0002-6778-7253)
- Jeffrey N. Martin (ORCID: https://orcid.org/0000-0002-9773-3256)
- Samuel R Schnittman (ORCID: https://orcid.org/0000-0002-9692-4405)
- Mabel P. Toribio (ORCID: https://orcid.org/0000-0002-4153-5568)
- Joseph A. Delaney (ORCID: https://orcid.org/0000-0003-1771-1776)
- Gabriele Beck‐Engeser
- Joseph J. Eron (ORCID: https://orcid.org/0000-0002-4938-0644)
- Kenneth Hugh Mayer (ORCID: https://orcid.org/0000-0001-7460-733X)
- Jeffrey M. Jacobson (ORCID: https://orcid.org/0000-0001-7250-1208)
- Pamela S. Douglas (ORCID: https://orcid.org/0000-0001-9876-4049)
- Steven Grinspoon (ORCID: https://orcid.org/0000-0002-6338-000X)
- Michael T. Lu (ORCID: https://orcid.org/0000-0003-4696-9610)
- Michael S. Saag (ORCID: https://orcid.org/0000-0002-8866-1043)
- Triin Umbleja (ORCID: https://orcid.org/0000-0001-7161-7743)
- Richard D. Moore (ORCID: https://orcid.org/0000-0001-8250-5069)
- Carlos Malvestutto (ORCID: https://orcid.org/0000-0003-3156-2965)
- Gerald S. Bloomfield (ORCID: https://orcid.org/0000-0002-7176-1611)
- Mari M. Kitahata (ORCID: https://orcid.org/0000-0002-5410-7175)
- Robin M. Nance (ORCID: https://orcid.org/0000-0002-4412-4844)
- Laura Bamford (ORCID: https://orcid.org/0009-0005-7192-6075)
- Marissa R Diggs
- Judith S. Currier (ORCID: https://orcid.org/0000-0003-4279-4737)
- Kathleen V. Fitch (ORCID: https://orcid.org/0000-0002-0541-3707)
- Sara McCallum (ORCID: https://orcid.org/0000-0002-0289-1295)
- Judith A. Aberg (ORCID: https://orcid.org/0000-0001-8162-0284)
- Gabrielle C. Ambayec
- Peter W. Hunt (ORCID: https://orcid.org/0000-0002-4571-4870)
Institutions
- University of North Carolina at Chapel Hill (US)
Publication Details
- Journal
- UNC Libraries
- Published
- 2025-09-24
- DOI
- https://doi.org/10.17615/q005-7w28
- Primary Topic
- Angiogenesis and VEGF in Cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00