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

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 UmblejaMichael 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

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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.

Original language	English
Journal	Open Forum Infectious Diseases
Volume	10
Issue number	10
DOIs	https://doi.org/10.1093/ofid/ofad467
State	Published - 1 Oct 2023

Keywords

HIV
VEGF
cancer
cardiovascular disease
neuropilin-1

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10.1093/ofid/ofad467

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Schnittman, S. R., Kolossváry, M., Beck-Engeser, G., Fitch, K. V., Ambayec, G. C., Nance, R. M., Zanni, M. V., Diggs, M., Chan, F., McCallum, S., Toribio, M., Bamford, L., Fichtenbaum, C. J., Eron, J. J., Jacobson, J. M., Mayer, K. H., Malvestutto, C., Bloomfield, G. S., Moore, R. D., ... Grinspoon, S. K. (2023). Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus. Open Forum Infectious Diseases, 10(10). https://doi.org/10.1093/ofid/ofad467

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

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",

author = "Schnittman, {Samuel R.} and M{\'a}rton Kolossv{\'a}ry and Gabriele Beck-Engeser and Fitch, {Kathleen V.} and Ambayec, {Gabrielle C.} and Nance, {Robin M.} and Zanni, {Markella V.} and Marissa Diggs and Fay Chan and Sara McCallum and Mabel Toribio and Laura Bamford and Fichtenbaum, {Carl J.} and Eron, {Joseph J.} and Jacobson, {Jeffrey M.} and Mayer, {Kenneth H.} and Carlos Malvestutto and Bloomfield, {Gerald S.} and Moore, {Richard D.} and Triin Umbleja and Saag, {Michael S.} and Aberg, {Judith A.} and Currier, {Judith S.} and Delaney, {Joseph A.C.} and Martin, {Jeffrey N.} and Lu, {Michael T.} and Douglas, {Pamela S.} and Ribaudo, {Heather J.} and Crane, {Heidi M.} and Hunt, {Peter W.} and Grinspoon, {Steven K.}",

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Schnittman, SR, Kolossváry, M, Beck-Engeser, G, Fitch, KV, Ambayec, GC, Nance, RM, Zanni, MV, Diggs, M, Chan, F, McCallum, S, Toribio, M, Bamford, L, Fichtenbaum, CJ, Eron, JJ, Jacobson, JM, Mayer, KH, Malvestutto, C, Bloomfield, GS, Moore, RD, Umbleja, T, Saag, MS, Aberg, JA, Currier, JS, Delaney, JAC, Martin, JN, Lu, MT, Douglas, PS, Ribaudo, HJ, Crane, HM, Hunt, PW & Grinspoon, SK 2023, 'Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus', Open Forum Infectious Diseases, vol. 10, no. 10. https://doi.org/10.1093/ofid/ofad467

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T1 - Biological and Clinical Implications of the Vascular Endothelial Growth Factor Coreceptor Neuropilin-1 in Human Immunodeficiency Virus

AU - Schnittman, Samuel R.

AU - Kolossváry, Márton

AU - Beck-Engeser, Gabriele

AU - Fitch, Kathleen V.

AU - Ambayec, Gabrielle C.

AU - Nance, Robin M.

AU - Zanni, Markella V.

AU - Diggs, Marissa

AU - Chan, Fay

AU - McCallum, Sara

AU - Toribio, Mabel

AU - Bamford, Laura

AU - Fichtenbaum, Carl J.

AU - Eron, Joseph J.

AU - Jacobson, Jeffrey M.

AU - Mayer, Kenneth H.

AU - Malvestutto, Carlos

AU - Bloomfield, Gerald S.

AU - Moore, Richard D.

AU - Umbleja, Triin

AU - Saag, Michael S.

AU - Aberg, Judith A.

AU - Currier, Judith S.

AU - Delaney, Joseph A.C.

AU - Martin, Jeffrey N.

AU - Lu, Michael T.

AU - Douglas, Pamela S.

AU - Ribaudo, Heather J.

AU - Crane, Heidi M.

AU - Hunt, Peter W.

AU - Grinspoon, Steven K.

PY - 2023/10/1

Y1 - 2023/10/1

N2 - 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.

AB - 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.

KW - HIV

KW - VEGF

KW - cancer

KW - cardiovascular disease

KW - neuropilin-1

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VL - 10

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ER -

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

Abstract

Keywords

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