Single-Cell RNA Sequencing Reveals Granzyme K⁺ CD8⁺ T Cells as a Target for Mitigating Plaque Instability Following...

Area of Science:

• Cardiovascular Research
• Immunology
• Radiotherapy Oncology

Background:

• Cardiac issues are rising in thoracic cancer patients with coronary disease post-radiotherapy.
• Mechanisms of radiotherapy-induced plaque instability and imaging changes are unclear.

Purpose of the Study:

• Identify key features of vulnerable plaques after radiotherapy using single-cell RNA sequencing.
• Investigate radiotherapy's impact on atherosclerotic lesions and immune cell dynamics.

Main Methods:

• Dual-mode OCT-IVUS imaging in rabbits to assess plaque stability.
• Single-cell RNA sequencing on atherosclerotic lesions from ApoE-/- mice.
• Bioinformatics, pathological staining, flow cytometry, gene knockout, and antibody depletion.

Main Results:

• OCT-IVUS accurately evaluated radiation effects on plaque stability.
• Single-cell transcriptomics revealed radiotherapy-induced immune remodeling.
• Identified a granzyme K+ CD8+ T-cell subpopulation expressing GZMB, exacerbating lesions.
• Absence of CD8+ T cells or GZMB ameliorated lesion progression.

Conclusions:

• Characteristic arterial imaging changes from radiation injury were identified.
• Radiation affects plaque stability via GZMK+ CD8+ T-cell activation and GZMB function.
• GZMB is a potential therapeutic target for radio-cardiovascular injury.