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

Samuel R SchnittmanMárton KolossváryGabriele Beck-EngeserKathleen V FitchGabrielle C AmbayecRobin M NanceMarkella V ZanniMarissa DiggsFay ChanSara McCallumMabel ToribioLaura BamfordCarl J FichtenbaumJoseph J EronJeffrey M JacobsonKenneth H MayerCarlos D MalvestuttoGerald S BloomfieldRichard D MooreTriin UmblejaMichael S SaagJudith A AbergJudith S CurrierJoseph A C DelaneyJeffrey N MartinMichael T LuPamela S DouglasHeather J RibaudoHeidi M CranePeter W HuntSteven K Grinspoon
Published in: Open forum infectious diseases (2023)
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.
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