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

Samuel R Schnittman; Márton Kolossváry; Gabriele Beck-Engeser; Kathleen V Fitch; Gabrielle C Ambayec; Robin M Nance; Markella V Zanni; Marissa Diggs; Fay Chan; Sara McCallum; Mabel Toribio; Laura Bamford; Carl J Fichtenbaum; Joseph J Eron; Jeffrey M Jacobson; Kenneth H Mayer; Carlos Malvestutto; Gerald S Bloomfield; Richard D Moore; Triin Umbleja; Michael S Saag; Judith A Aberg; Judith S Currier; Joseph A C Delaney; Jeffrey N Martin; Michael T Lu; Pamela S Douglas; Heather J Ribaudo; Heidi M Crane; Peter W Hunt; Steven K Grinspoon

doi:10.1093/ofid/ofad467

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

Open Forum Infect Dis. 2023 Sep 8;10(10):ofad467. doi: 10.1093/ofid/ofad467. eCollection 2023 Oct.

Authors

Samuel R Schnittman^{1

2}, Márton Kolossváry², Gabriele Beck-Engeser³, Kathleen V Fitch², Gabrielle C Ambayec³, Robin M Nance⁴, Markella V Zanni², Marissa Diggs², Fay Chan³, Sara McCallum², Mabel Toribio², Laura Bamford⁵, Carl J Fichtenbaum⁶, Joseph J Eron⁷, Jeffrey M Jacobson⁸, Kenneth H Mayer⁹, Carlos Malvestutto¹⁰, Gerald S Bloomfield¹¹, Richard D Moore¹², Triin Umbleja¹³, Michael S Saag¹⁴, Judith A Aberg¹⁵, Judith S Currier¹⁶, Joseph A C Delaney^{17

18}, Jeffrey N Martin¹⁹, Michael T Lu²⁰, Pamela S Douglas¹², Heather J Ribaudo¹⁴, Heidi M Crane⁴, Peter W Hunt³, Steven K Grinspoon²

Affiliations

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

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.

Keywords: HIV; VEGF; cancer; cardiovascular disease; neuropilin-1.

Associated data

ClinicalTrials.gov/NCT02344290

Abstract

Associated data

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