Impaired CD4+ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles
4 affiliations
- 1Department of Cardiology, Oppenheimer Atherosclerosis Research Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States
- 2Department of Cardiology, Barbra Streisand Women’s Heart Center, Smidt Heart Institute, Los Angeles, California, United States
- 3Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, United States
- 4Department of Biomedical Engineering, University of Southern California, Los Angeles, California, United States
Abstract
The apolipoprotein B-100 (ApoB-100) peptide P210 (amino acids 3136–3155) is localized within atherosclerotic plaques, and low IgG autoantibody levels against P210 are associated with a higher risk of plaque rupture and myocardial infarction (MI), suggesting that this humoral immunity is protective in atherosclerotic cardiovascular disease (ASCVD). Although the clinical significance of P210 antibody response has been shown, it remains unclear whether patients with ASCVD also exhibit an impaired T cell response to P210. Thus, we investigated the T cell response to P210 in patients with ASCVD and evaluated its potential as a target for therapeutic intervention. Peripheral blood mononuclear cells (PBMCs) collected from patients with ASCVD and controls were stimulated with the P210 peptide and evaluated for T cell responses using the activated immune markers (AIM) assay. PBMCs from patients with ASCVD stimulated with P210 had a significantly impaired CD4+CD69+CD154+ T cell response, which persisted into follow-up a year later. Significantly reduced CD4+ T follicular helper cell responses to P210 were also noted in patients with ASCVD. Given the beneficial immunomodulation by P210 nanoparticles (P210-PAM) that resulted in reduced atherosclerosis in mice, we investigated its effect on PBMCs from patients with ASCVD. Treatment with P210-PAM significantly improved the impaired CD4+CD69+CD154+ and CD4+CD134+CD137+ T cell activation in response to P210. The study suggests potential future clinical translation for P210-PAM as an immune-modulation strategy for ASCVD.
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BibTeX
@article{dimayuga2026impaired,
title = {{Impaired CD4+ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles}},
author = {Paul C. Dimayuga and Jianchang Zhou and Xiaoning Zhao and Janet Wei and Noah Trac and Karla Lambaren and Eun Ji Chung and Bojan Cercek and Prediman K. Shah and Kuang-Yuh Chyu},
journal = {American journal of physiology. Heart and circulatory physiology},
year = {2026},
month = aug,
doi = {10.1152/ajpheart.00406.2026},
url = {https://doi.org/10.1152/ajpheart.00406.2026},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Impaired CD4+ T cell response to apolipoprotein B-100 peptide P210 in atherosclerotic cardiovascular disease is reversed by P210-conjugated nanoparticles
AU - Paul C. Dimayuga
AU - Jianchang Zhou
AU - Xiaoning Zhao
AU - Janet Wei
AU - Noah Trac
AU - Karla Lambaren
AU - Eun Ji Chung
AU - Bojan Cercek
AU - Prediman K. Shah
AU - Kuang-Yuh Chyu
PY - 2026
DA - 2026/08/21
JO - American journal of physiology. Heart and circulatory physiology
DO - 10.1152/ajpheart.00406.2026
UR - https://doi.org/10.1152/ajpheart.00406.2026
AB - The apolipoprotein B-100 (ApoB-100) peptide P210 (amino acids 3136–3155) is localized within atherosclerotic plaques, and low IgG autoantibody levels against P210 are associated with a higher risk of plaque rupture and myocardial infarction (MI), suggesting that this humoral immunity is protective in atherosclerotic cardiovascular disease (ASCVD). Although the clinical significance of P210 antibody response has been shown, it remains unclear whether patients with ASCVD also exhibit an impaired T cell response to P210. Thus, we investigated the T cell response to P210 in patients with ASCVD and evaluated its potential as a target for therapeutic intervention. Peripheral blood mononuclear cells (PBMCs) collected from patients with ASCVD and controls were stimulated with the P210 peptide and evaluated for T cell responses using the activated immune markers (AIM) assay. PBMCs from patients with ASCVD stimulated with P210 had a significantly impaired CD4+CD69+CD154+ T cell response, which persisted into follow-up a year later. Significantly reduced CD4+ T follicular helper cell responses to P210 were also noted in patients with ASCVD. Given the beneficial immunomodulation by P210 nanoparticles (P210-PAM) that resulted in reduced atherosclerosis in mice, we investigated its effect on PBMCs from patients with ASCVD. Treatment with P210-PAM significantly improved the impaired CD4+CD69+CD154+ and CD4+CD134+CD137+ T cell activation in response to P210. The study suggests potential future clinical translation for P210-PAM as an immune-modulation strategy for ASCVD.
SN - 0363-6135
SN - 1522-1539
ER -