Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus
Open Forum Infectious Diseases, 2023
Schnittman S., Kolossváry M., Beck-Engeser G., Fitch K., Ambayec G., Nance R., Zanni M., Diggs M., Chan F., McCallum S., Toribio M., Bamford L., Fichtenbaum C., Eron J., Jacobson J., Mayer K., Malvestutto C., Bloomfield G., Moore R., Umbleja T., Saag M., Aberg J., Currier J., Delaney J., Martin J., Lu M., Douglas P., Ribaudo H., Crane H., Hunt P., Grinspoon S.
| Disease area | Application area | Sample type | Products |
|---|---|---|---|
CVD Infectious Diseases | Pathophysiology | Plasma |  Olink Target 96 |
Abstract
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.
Clinical Trials Registration. NCT02344290.