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Real-Time Monitoring of Intraplaque Furin in Atherosclerotic Mice during Pneumonia and Dexamethasone Treatment
Fang-Kun Yang1,2, Rui Chen1,2, Chen-Hui Zhou1
1Department of Cardiology, First Affiliated Hospital of Ningbo University, School of Medicine, Ningbo University, Ningbo 315211, China.
Abstract:
Atherosclerotic plaque destabilization during acute infections such as pneumonia represents a critical clinical challenge, yet the underlying molecular dynamics remain poorly characterized. This study introduces a furin-responsive photoacoustic/fluorescence dual-modal probe (FRP) to investigate intraplaque furin activity in ApoE-/- mice with pneumonia-complicated atherosclerosis. The FRP, integrating photoacoustic and fluorescence imaging modalities, enabled comprehensive longitudinal monitoring of plaque furin dynamics both in vitro and in vivo. Notably, dexamethasone treatment effectively reduced plaque furin content, demonstrating the reversibility of this inflammatory response. Histopathological analysis confirmed that furin upregulation correlated with increased plaque inflammation, extracellular matrix degradation, and necrotic core expansion. These findings establish in vivo furin imaging as a valuable approach for elucidating the mechanistic links between systemic inflammation and plaque vulnerability and for evaluating therapeutic interventions aimed at plaque stabilization.
Insights
This study developed a novel probe to track furin activity in atherosclerotic plaques during pneumonia. Dexamethasone treatment reduced plaque furin, showing potential for stabilizing vulnerable plaques.
Area of Science:
- Biomedical Imaging
- Cardiovascular Research
- Molecular Biology
Background:
- Atherosclerotic plaque destabilization during infections like pneumonia is a clinical problem.
- The molecular mechanisms linking infection-induced inflammation to plaque vulnerability are not well understood.
- Furin, a protease, is implicated in inflammation and extracellular matrix degradation.
Purpose of the Study:
- To develop and utilize a dual-modal imaging probe for in vivo assessment of intraplaque furin activity.
- To investigate the role of furin in pneumonia-complicated atherosclerosis in ApoE-/- mice.
- To evaluate the effect of dexamethasone on intraplaque furin levels and plaque characteristics.
Main Methods:
- Development of a furin-responsive photoacoustic/fluorescence dual-modal probe (FRP).
- In vitro and in vivo imaging of plaque furin dynamics in ApoE-/- mice with induced pneumonia.
- Administration of dexamethasone to assess therapeutic effects.
- Histopathological analysis of atherosclerotic plaques.
Main Results:
- The FRP successfully enabled longitudinal monitoring of intraplaque furin activity in vivo.
- Dexamethasone treatment significantly reduced plaque furin content, indicating reversibility.
- Increased furin levels correlated with heightened plaque inflammation, ECM degradation, and necrotic core expansion.
- Established a link between systemic inflammation and plaque vulnerability.
Conclusions:
- In vivo furin imaging is a valuable tool for studying atherosclerosis.
- Furin plays a significant role in infection-exacerbated plaque destabilization.
- Therapeutic strategies targeting furin may stabilize vulnerable atherosclerotic plaques.
