The plaque-aortic ring assay: a new method to study human atherosclerosis-induced angiogenesis

Area of Science:

• Cardiovascular Biology
• Vascular Biology
• Translational Medicine

Background:

• Atherosclerotic plaque progression is linked to angiogenesis, contributing to intraplaque hemorrhages and instability.
• Current models inadequately represent human plaque-induced angiogenesis, hindering research progress.

Purpose of the Study:

• To introduce a novel ex vivo model for studying human plaque-induced angiogenesis.
• To investigate the cellular and molecular mechanisms driving neovascularization in atherosclerotic plaques.

Main Methods:

• Human atherosclerotic plaques from endarterectomy patients were co-cultured with rat aorta rings in collagen gels.
• Angiogenic activity was assessed by sprouting from aortic rings, and macrophage outgrowth from adventitia was monitored.
• Proteomic analysis of plaque secretomes and antibody-mediated VEGF blockade were performed.

Main Results:

• Human plaque fragments significantly stimulated angiogenesis and macrophage outgrowth from rat aortic rings.
• Stimulatory activity correlated with intraplaque macrophage presence.
• VEGF blockade showed transient inhibition, suggesting redundant angiogenic stimuli; adventitial macrophage ablation permanently impaired angiogenesis.

Conclusions:

• The developed ex vivo model effectively reproduces human plaque-induced angiogenesis using rat aortic rings.
• This model facilitates the identification of key mechanisms in atherosclerotic plaque neovascularization.
• Macrophages play a critical role in mediating plaque-induced angiogenesis.