Exploring the relationship between hemodynamics and the immune microenvironment in carotid atherosclerosis: Insights
Xiaolong Ya1,2, Long Ma1,2, Hao Li1,2
1Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
This study reveals how blood flow patterns influence immune cells in carotid atherosclerosis. Adverse flow promotes neutrophils and specific macrophage types, impacting plaque progression and offering new therapeutic targets.
Area of Science:
- Cardiovascular Research
- Immunology
- Biomedical Engineering
Background:
- Carotid atherosclerosis, a primary cause of stroke, involves complex interactions between hemodynamic forces and the immune microenvironment.
- Existing research lacks a comprehensive understanding of how specific hemodynamic conditions influence immune cell dynamics in atherosclerotic plaques.
- Immune cell alterations are central to plaque formation and progression, influenced by various external factors.
Purpose of the Study:
- To investigate the intricate relationship between hemodynamic forces and the immune microenvironment in carotid atherosclerosis.
- To explore how different hemodynamic conditions, such as wall shear stress (WSS) and oscillatory shear index (OSI), affect immune cell populations within plaques.
- To identify potential immune-related therapeutic targets for atherosclerosis based on hemodynamic influences.
Main Methods:
- Integration of computational fluid dynamics (CFD) for hemodynamic analysis.
- Application of Mass cytometry (CyTOF) for high-dimensional immune cell profiling within plaques.
- Correlation of specific hemodynamic parameters (WSS, OSI) with distinct immune cell subsets.
Main Results:
- Neutrophils were significantly enriched in adverse hemodynamic environments.
- Distinct macrophage populations were identified: M2-like CD163+CD86+ macrophages in high WSS/low OSI areas, and CD163-CD14+ macrophages in low WSS/high OSI areas.
- Evidence of T cell pro-inflammatory activation, dysregulation, and an M1/M2 macrophage imbalance was observed in response to adverse flow patterns.
Conclusions:
- Hemodynamic forces critically regulate the immune cell composition and function within carotid atherosclerotic plaques.
- Adverse flow patterns promote an inflammatory immune microenvironment, potentially driving plaque progression.
- Understanding these hemodynamics-immunity interactions offers novel insights and potential targets for precision therapies in atherosclerosis treatment.
Abstract:
Carotid atherosclerosis is a major cause of stroke. Hemodynamic forces, such as shear stress and oscillatory shear, play an important role in the initiation and progression of atherosclerosis. The alteration of the immune microenvironment is the fundamental pathological mechanism by which diverse external environmental factors impact the formation and progression of plaques. However, Current research on the relationship between hemodynamics and immunity in atherosclerosis still lack of comprehensive understanding. In this study, we combined computational fluid dynamics (CFD) and Mass cytometry (CyTOF) technologies to explore the changes in the immune microenvironment within plaques under different hemodynamic conditions. Our results indicated that neutrophils were enriched in adverse flow environments. M2-like CD163+CD86+ macrophages were predominantly enriched in high WSS and low OSI environments, while CD163-CD14+ macrophages were enriched in low WSS and high OSI environments. Functional analysis further revealed T cell pro-inflammatory activation and dysregulation in modulation, along with an imbalance in M1-like/M2-like macrophages, suggesting their potential involvement in the progression of atherosclerotic lesions mediated by adverse flow patterns. Our study elucidated the potential mechanisms by which hemodynamics regulated the immune microenvironment within plaques, providing intervention targets for future precision therapies.
