Is there life after plaque rupture?

Area of Science:

• Cardiovascular Biology
• Atherosclerosis Research
• Vascular Remodelling

Background:

• The interplay between atherosclerotic plaque stability and adaptive vascular geometric remodelling remains poorly understood.
• Unstable atherosclerosis poses significant clinical challenges, highlighting the need to investigate plaque rupture mechanisms.

Purpose of the Study:

• To investigate the relationship between plaque rupture and adaptive geometric remodelling in the brachiocephalic arteries of mice.
• To determine the influence of plaque stability and outward remodelling on plaque rupture.
• To assess the effect of pravastatin on plaque stability and remodelling dynamics.

Main Methods:

• Utilized fat-fed apolipoprotein E (apoE)-knockout mice to study atherosclerosis.
• Assessed vessel expansive remodelling in brachiocephalic arteries with and without plaques.
• Quantified plaque stability, fibrous cap thickness, and lumen area changes over time.
• Evaluated the impact of pravastatin treatment on remodelling and plaque rupture incidence.

Main Results:

• Vessel expansive remodelling rates were similar in vessels with and without plaques, indicating plaque presence is not required for remodelling.
• Expansive remodelling was strongly associated with plaque stability; stable plaques showed no expansion, while ruptured plaques exhibited significant expansion.
• Stable plaques led to lumen loss, whereas unstable plaques maintained lumen area.
• Pravastatin increased fibrous cap thickness, enhanced vessel expansion, and prolonged the interval between plaque ruptures without altering overall remodelling rates.

Conclusions:

• Vessel expansion in this model is independent of plaque presence and is a key driver of plaque rupture.
• Plaque rupture occurs when outward remodelling forces exceed the plaque's cap strength.
• Therapeutic interventions like pravastatin can strengthen plaques, increasing resistance to rupture by allowing greater outward remodelling.