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Plaque fissure: the link between atherosclerosis and thrombosis
C Lendon1, G V Born, M J Davies
1William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, UK.
Insights
Atheromatous plaque cap rupture exposes lipids, initiating arterial thrombosis and potentially causing heart attacks. Circulating catecholamines influence lipid uptake, while macrophages may contribute to plaque instability and fissure formation.
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Thrombosis Mechanisms
Background:
- Arterial thrombosis, particularly coronary thrombosis, is primarily caused by the rupture of atheromatous plaque caps.
- This rupture exposes plaque contents like collagen and lipids, triggering platelet aggregation and blood coagulation.
- Clinical events such as unstable angina and myocardial infarction are linked to this thrombotic process.
Purpose of the Study:
- To investigate the early development of atheromatous plaques prone to fissuring.
- To identify factors influencing lipid accumulation within plaque caps.
- To explore the causes of plaque fissure formation.
Main Methods:
- Review of angiograms from patients with unstable angina and myocardial infarction.
- Direct angioscopy to visualize thrombi on fissured plaques in coronary arteries.
- Investigating the role of circulating catecholamines in low-density lipoprotein uptake into plaques.
- Analyzing plaque cap composition, including macrophage concentration.
Main Results:
- Circulating catecholamine concentration is a factor promoting lipid uptake into atheromatous plaques.
- Evidence suggests a complex interplay of determinants causes plaque fissure.
- Macrophage concentration within plaque caps is implicated in plaque fissuring.
Conclusions:
- Plaque cap integrity is crucial in preventing arterial thrombosis.
- Catecholamines play a role in the lipid accumulation phase of atherogenesis.
- Macrophage presence in plaque caps is a significant factor in plaque instability and rupture.
Abstract:
The immediate cause of arterial, predominantly coronary thrombosis is almost always cracking or fissuring of the cap of an atheromatous plaque. This exposes collagen and lipids to the flowing blood and thereby initiates thrombotic platelet aggregation, almost immediately followed by coagulation. The thrombi tend to extend into the arterial lumen, causing obstruction to blood flow and clinical symptoms and signs. Evidence for this sequence of events comes, inter alia, from angiograms of patients with unstable angina and developing myocardial infarction. Direct angioscopy in life is also visualising mural thrombi over fissured plaques in atheromatous coronary arteries. We are investigating the initial development of atheromatous plaques liable to fissuring. The cap over such plaques covers a "lipid pool". We have discovered that one factor promoting the uptake of lipid, in the form of plasma low-density lipoprotein, is the concentration of circulating catecholamines (Cardona-Sanclemente LE, Gorog P, Born GVR (1992) J Physiol London, in press). We are also investigating the immediate cause(s) of plaque fissure. We have evidence for a complex interaction of different determinants, including the concentration of macrophages, presumably as foam cells, in the plaque caps (Lendon CL, Davies MJ, Born BVR, Richardson PD (1991) Atherosclerosis 87: 87).