학술논문
Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus
Document Type
article
Author
Schnittman, Samuel R; Kolossváry, Márton; Beck-Engeser, Gabriele; Fitch, Kathleen V; Ambayec, Gabrielle C; Nance, Robin M; Zanni, Markella V; Diggs, Marissa; Chan, Fay; McCallum, Sara; Toribio, Mabel; Bamford, Laura; Fichtenbaum, Carl J; Eron, Joseph J; Jacobson, Jeffrey M; Mayer, Kenneth H; Malvestutto, Carlos; Bloomfield, Gerald S; Moore, Richard D; Umbleja, Triin; Saag, Michael S; Aberg, Judith A; Currier, Judith S; Delaney, Joseph AC; Martin, Jeffrey N; Lu, Michael T; Douglas, Pamela S; Ribaudo, Heather J; Crane, Heidi M; Hunt, Peter W; Grinspoon, Steven K
Source
Open Forum Infectious Diseases. 10(10)
Subject
Language
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.