Related Experiment Videos
Pathophysiology of plaque rupture and the concept of plaque stabilization
1Division of Cardiology and the Atherosclerosis Research Center, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Insights
Atherosclerosis plaque rupture causes acute coronary syndromes. Stabilizing vulnerable plaques through interventions may reduce these life-threatening events, offering a new treatment paradigm.
Area of Science:
- Cardiovascular Medicine
- Pathology
- Biomedical Engineering
Background:
- Acute coronary syndromes (ACS) are often caused by atherosclerosis plaque rupture and thrombosis.
- Vulnerable plaques feature lipid-rich cores, thin fibrous caps, and inflammatory cells, making them prone to rupture.
- Plaque rupture is linked to concentrated biomechanical and hemodynamic stresses at weak points.
Purpose of the Study:
- To explore the concept of plaque stabilization as a strategy to reduce acute coronary syndromes.
- To review the factors contributing to plaque vulnerability and rupture.
- To assess the potential of plaque stabilization as a therapeutic approach.
Main Methods:
- Review of pathological features of vulnerable atherosclerotic plaques.
- Analysis of biomechanical and hemodynamic factors influencing plaque stability.
- Evaluation of indirect clinical trial data supporting plaque stabilization.
Main Results:
- Plaque characteristics (lipid core, thin cap, inflammation) predict rupture risk.
- Mechanical stresses concentrate at vulnerable sites, promoting disruption.
- Lipid-lowering and lifestyle modifications indirectly support plaque stabilization.
Conclusions:
- Plaque stabilization is a promising concept for reducing ACS incidence.
- Targeting endothelial dysfunction and plaque vulnerability may prevent rupture and thrombosis.
- Further human validation is needed, but current evidence supports plaque stabilization as a key therapeutic goal.
Abstract:
Atherosclerosis complicated by plaque rupture or disruption and thrombosis is primarily responsible for the potentially lethal acute coronary syndromes. Plaques with a large extracellular lipid-rich core, thin fibrous cap with reduced collagen content and smooth muscle density, and increased numbers of activated macrophages and mast cells appear to be most vulnerable to rupture. Plaque disruption tends to occur at points at which the plaque surface is weakest and most vulnerable, which coincide with points at which stresses, resulting from biomechanical and hemodynamic forces acting on plaques, are concentrated. Reduced matrix synthesis as well as increased matrix degradation may predispose fibrous caps to rupture spontaneously or in response to extrinsic mechanical or hemodynamic stresses. Modification of endothelial dysfunction and reduction of vulnerability to plaque rupture and thrombosis may lead to plaque stabilization resulting in reduction of the frequency of acute coronary syndromes. This putative concept of plaque stabilization, although attractive, has not yet been rigorously validated in humans. Indirect data from clinical trials involving lipid lowering/modification and lifestyle/risk factor modification, however, provide strong support for this new paradigm. Thus, plaque stabilization may prove to be an important modality for reduction of lethal consequences of coronary atherosclerosis.