Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus

Author:

Schnittman Samuel R12ORCID,Kolossváry Márton2,Beck-Engeser Gabriele3,Fitch Kathleen V2,Ambayec Gabrielle C3,Nance Robin M4,Zanni Markella V2,Diggs Marissa2,Chan Fay3,McCallum Sara2,Toribio Mabel2,Bamford Laura5,Fichtenbaum Carl J6,Eron Joseph J7,Jacobson Jeffrey M8,Mayer Kenneth H9,Malvestutto Carlos10ORCID,Bloomfield Gerald S11,Moore Richard D12,Umbleja Triin13,Saag Michael S14ORCID,Aberg Judith A15,Currier Judith S16ORCID,Delaney Joseph A C1718,Martin Jeffrey N19,Lu Michael T20,Douglas Pamela S12,Ribaudo Heather J14,Crane Heidi M4,Hunt Peter W3,Grinspoon Steven K2

Affiliation:

1. Division of Infectious Diseases, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts , USA

2. Metabolism Unit, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts , USA

3. Division of Experimental Medicine, University of California, San Francisco , San Francisco, California , USA

4. Department of Medicine, University of Washington , Seattle, Washington , USA

5. Division of Infectious Diseases and Global Public Health, University of California, San Diego , San Diego, California , USA

6. Division of Infectious Diseases, University of Cincinnati , Cincinnati, Ohio , USA

7. Division of Infectious Diseases, University of North Carolina , Chapel Hill, North Carolina , USA

8. Division of Infectious Diseases, Case Western Reserve University , Cleveland, Ohio , USA

9. Fenway Health and Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School , Boston, Massachusetts , USA

10. Division of Infectious Diseases, The Ohio State University Wexner Medical Center , Columbus, Ohio , USA

11. Duke Clinical Research Institute, Duke University , Durham, North Carolina , USA

12. Division of Infectious Diseases, Johns Hopkins University School of Medicine , Baltimore, Maryland , USA

13. Harvard T. H. Chan School of Public Health, Harvard University , Boston, Massachusetts , USA

14. Division of Infectious Diseases, University of Alabama at Birmingham , Birmingham, Alabama , USA

15. Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai , New York, New York , USA

16. Division of Infectious Diseases, University of California, Los Angeles , Los Angeles, California , USA

17. Department of Epidemiology, University of Washington , Seattle, Washington , USA

18. College of Pharmacy, University of Manitoba , Winnipeg, Manitoba , Canada

19. Department of Epidemiology and Biostatistics, University of California, San Francisco School of Medicine , San Francisco, California , USA

20. Cardiovascular Imaging Research Center, Department of Radiology, Massachusetts General Hospital and Harvard Medical School , Boston, Massachusetts , USA

Abstract

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.

Funder

National Institutes of Health

REPRIEVE Clinical Coordinating Center

REPRIEVE Data Coordinating Center)

Kowa Pharmaceuticals

Gilead Sciences

ViiV Healthcare

NIAID

ACTG Leadership and Operations Center

ACTG Laboratory Center

(CNICS)

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Oncology

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