Altered Immune Profiles in Non‐Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy
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| Format: | Artículo Open Access |
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2025
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| _version_ | 1867015279932866560 |
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| author | Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian |
| author_facet | Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian |
| collection | Wiley Open Access |
| contents | Altered Immune Profiles in Non‐Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian Clinical Transplantation ABSTRACT Introduction Cardiac allograft vasculopathy (CAV) develops more aggressively in recipients of hearts from brain‐dead (BD) donors with induced long QT syndrome (iLQTS), yet the underlying mechanisms remain poorly understood. In this study, we employ a multi‐omics and experimental framework to explore the role of neuro‐immune interactions in non‐failing donor hearts affected by iLQTS. Methods Single‐nuclei RNA sequencing (snRNA‐seq) compared four iLQTS and four non‐arrhythmic non‐failing donor hearts. Pathway enrichment and cell‐cell communication were assessed. Plasma proteome data from BD donors and neuronal differentially expressed (DE) genes were integrated via Omicsnet. Human BD donor transcriptomes data were analyzed for immune correlation. Results ILQTS hearts showed elevated T/mast cells and upregulated leukocyte migration/focal adhesion pathways. Neuronal signaling (NGF, HSPG) and adhesion molecules (ITGB1, LAMININ) drove immune trafficking. Integrative proteomics identified ITGB1 as a central hub linking neuronal DE genes to BD‐associated plasma proteins. Human validation linked activated CD4 + T cells/Th2 enrichment to prolonged QT intervals. Conclusions Neuro‐immune dysregulation and integrin signaling related T cell activation underlie iLQTS‐related heart donors. Targeting neuronal‐integrin crosstalk may reduce CAV progression and improve transplant outcomes. 10.1111/ctr.70286 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| doi_str_mv | 10.1111/ctr.70286 |
| format | Artículo Open Access |
| id | wiley_oa_10_1111_ctr_70286 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| publishDate | 2025 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Altered Immune Profiles in Non‐Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian Clinical Transplantation Altered Immune Profiles in Non‐Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy Zhi Wen Shuai Shao Yu Feng Zheng Wang Jianqiang Wu Changxue Wu Mingwu Tian Clinical Transplantation ABSTRACT Introduction Cardiac allograft vasculopathy (CAV) develops more aggressively in recipients of hearts from brain‐dead (BD) donors with induced long QT syndrome (iLQTS), yet the underlying mechanisms remain poorly understood. In this study, we employ a multi‐omics and experimental framework to explore the role of neuro‐immune interactions in non‐failing donor hearts affected by iLQTS. Methods Single‐nuclei RNA sequencing (snRNA‐seq) compared four iLQTS and four non‐arrhythmic non‐failing donor hearts. Pathway enrichment and cell‐cell communication were assessed. Plasma proteome data from BD donors and neuronal differentially expressed (DE) genes were integrated via Omicsnet. Human BD donor transcriptomes data were analyzed for immune correlation. Results ILQTS hearts showed elevated T/mast cells and upregulated leukocyte migration/focal adhesion pathways. Neuronal signaling (NGF, HSPG) and adhesion molecules (ITGB1, LAMININ) drove immune trafficking. Integrative proteomics identified ITGB1 as a central hub linking neuronal DE genes to BD‐associated plasma proteins. Human validation linked activated CD4 + T cells/Th2 enrichment to prolonged QT intervals. Conclusions Neuro‐immune dysregulation and integrin signaling related T cell activation underlie iLQTS‐related heart donors. Targeting neuronal‐integrin crosstalk may reduce CAV progression and improve transplant outcomes. 10.1111/ctr.70286 http://creativecommons.org/licenses/by-nc-nd/4.0/ |
| title | Altered Immune Profiles in Non‐Failing Heart Donors With Induced Long QT Syndrome: A Potential Risk Factor for Cardiac Allograft Vasculopathy |
| topic | Clinical Transplantation |
| url | https://onlinelibrary.wiley.com/doi/10.1111/ctr.70286 |