Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure

Tess E. Peterson; Virginia S. Hahn; Ruin Moaddel; Min Zhu; Sabina A. Haberlen; Frank J. Palella; Michael Plankey; Joel S. Bader; Joao A.C. Lima; Robert E. Gerszten; Jerome I. Rotter; Stephen S. Rich; Susan R. Heckbert; Gregory D. Kirk; Damani A. Piggott; Luigi Ferrucci; Joseph B. Margolick; Todd T. Brown; Katherine C. Wu; Wendy S. Post

doi:10.1038/s41467-025-55911-0

Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure

Tess E. Peterson^*, Virginia S. Hahn, Ruin Moaddel, Min Zhu, Sabina A. Haberlen, Frank J. Palella, Michael Plankey, Joel S. Bader, Joao A.C. Lima, Robert E. Gerszten, Jerome I. Rotter, Stephen S. Rich, Susan R. Heckbert, Gregory D. Kirk, Damani A. Piggott, Luigi Ferrucci, Joseph B. Margolick, Todd T. Brown, Katherine C. Wu, Wendy S. Post

^*Corresponding author for this work

Medicine, Infectious Diseases Division

Research output: Contribution to journal › Article › peer-review

Abstract

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a plasma proteomic signature that may in part reflect or contribute to HIV-associated atrial remodeling, many features of which are associated with older age and time to incident heart failure among an independent community-based cohort without HIV. This proteomic profile was statistically enriched for immune checkpoint proteins, tumor necrosis factor signaling, ephrin signaling, and extracellular matrix organization, identifying possible shared pathways in HIV and aging that may contribute to risk of heart failure.

Original language	English (US)
Article number	610
Journal	Nature communications
Volume	16
Issue number	1
DOIs	https://doi.org/10.1038/s41467-025-55911-0
State	Published - Dec 2025

Funding

This study was supported in part by the National Institutes of Health (NIH: R01 HL126552 (SMASH study, K.C.W. and W.S.P.); U01-DA036297 (ALIVE data collection); and U01-HL146201, U01-HL146193, U01-HL146240, and U01-HL146205 (MACS, WIHS data collection). Proteomics was supported by U01HL146201, Johns Hopkins University Center for AIDS Research (P30AI094189), the Intramural Research Program of the National Institute on Aging, NIH (ZIAAG000297), and Dr. Nancy Grasmick. Support for the Multi-Ethnic Study of Atherosclerosis (MESA) projects are conducted and supported by the National Heart, Lung, and Blood Institute (NHLBI) in collaboration with MESA investigators. Support for MESA is provided by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, N01-HC-95169, UL1-TR-000040, UL1-TR-001079, UL1-TR-001420, UL1TR001881, DK063491, and R01HL105756. Molecular data for the Trans-Omics in Precision Medicine (TOPMed) program was supported by the NHLBI. Proteomics was supported by TOPMed MESA Multi-Omics (HHSN2682015000031, HSN26800004, HHSN268201600034I). Core support, including centralized genomic read mapping and genotype calling, along with variant quality metrics and filtering were provided by the TOPMed Informatics Research Center (3R01HL-117626-02S1; contract HHSN268201800002I). Core support, including phenotype harmonization, data management, sample-identity QC, and general program coordination, was provided by the TOPMed Data Coordinating Center (R01HL-120393; U01HL-120393; contract HHSN268201800001I). TEP is supported by NIH/NHLBI T32 HL007227. T.T.B. is supported in part by K24 AI120834. V.S.H. is supported by NIH NHLBI 1K23HL166770-01 and the Sarnoff Scholar Award 138828. The authors gratefully acknowledge the contributions of the study participants and the dedication of the MWCCS, ALIVE, SMASH, and MESA-TOPMed investigators and staff. Full MWCCS acknowledgement may be found at https://statepi.jhsph.edu/mwccs/acknowledgements/ . A full list of participating MESA investigators and institutes can be found at http://www.mesa-nhlbi.org . We would also like to thank Jinshui Fan and Giovanna Fantoni for their help in the Olink proteomic analysis.

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Peterson, T. E., Hahn, V. S., Moaddel, R., Zhu, M., Haberlen, S. A., Palella, F. J., Plankey, M., Bader, J. S., Lima, J. A. C., Gerszten, R. E., Rotter, J. I., Rich, S. S., Heckbert, S. R., Kirk, G. D., Piggott, D. A., Ferrucci, L., Margolick, J. B., Brown, T. T., Wu, K. C., & Post, W. S. (2025). Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure. Nature communications, 16(1), Article 610. https://doi.org/10.1038/s41467-025-55911-0

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title = "Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure",

abstract = "People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a plasma proteomic signature that may in part reflect or contribute to HIV-associated atrial remodeling, many features of which are associated with older age and time to incident heart failure among an independent community-based cohort without HIV. This proteomic profile was statistically enriched for immune checkpoint proteins, tumor necrosis factor signaling, ephrin signaling, and extracellular matrix organization, identifying possible shared pathways in HIV and aging that may contribute to risk of heart failure.",

author = "Peterson, {Tess E.} and Hahn, {Virginia S.} and Ruin Moaddel and Min Zhu and Haberlen, {Sabina A.} and Palella, {Frank J.} and Michael Plankey and Bader, {Joel S.} and Lima, {Joao A.C.} and Gerszten, {Robert E.} and Rotter, {Jerome I.} and Rich, {Stephen S.} and Heckbert, {Susan R.} and Kirk, {Gregory D.} and Piggott, {Damani A.} and Luigi Ferrucci and Margolick, {Joseph B.} and Brown, {Todd T.} and Wu, {Katherine C.} and Post, {Wendy S.}",

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year = "2025",

month = dec,

doi = "10.1038/s41467-025-55911-0",

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Peterson, TE, Hahn, VS, Moaddel, R, Zhu, M, Haberlen, SA, Palella, FJ, Plankey, M, Bader, JS, Lima, JAC, Gerszten, RE, Rotter, JI, Rich, SS, Heckbert, SR, Kirk, GD, Piggott, DA, Ferrucci, L, Margolick, JB, Brown, TT, Wu, KC & Post, WS 2025, 'Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure', Nature communications, vol. 16, no. 1, 610. https://doi.org/10.1038/s41467-025-55911-0

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T1 - Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure

AU - Peterson, Tess E.

AU - Hahn, Virginia S.

AU - Moaddel, Ruin

AU - Zhu, Min

AU - Haberlen, Sabina A.

AU - Palella, Frank J.

AU - Plankey, Michael

AU - Bader, Joel S.

AU - Lima, Joao A.C.

AU - Gerszten, Robert E.

AU - Rotter, Jerome I.

AU - Rich, Stephen S.

AU - Heckbert, Susan R.

AU - Kirk, Gregory D.

AU - Piggott, Damani A.

AU - Ferrucci, Luigi

AU - Margolick, Joseph B.

AU - Brown, Todd T.

AU - Wu, Katherine C.

AU - Post, Wendy S.

PY - 2025/12

Y1 - 2025/12

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AB - People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a plasma proteomic signature that may in part reflect or contribute to HIV-associated atrial remodeling, many features of which are associated with older age and time to incident heart failure among an independent community-based cohort without HIV. This proteomic profile was statistically enriched for immune checkpoint proteins, tumor necrosis factor signaling, ephrin signaling, and extracellular matrix organization, identifying possible shared pathways in HIV and aging that may contribute to risk of heart failure.

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Proteomic signature of HIV-associated subclinical left atrial remodeling and incident heart failure

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