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The interface of atherosclerosis and thrombosis: basic mechanisms
1Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Insights
Atherosclerosis involves plaque disruption, leading to thrombosis and occlusive vascular disease. Inflammation and coagulation factors play key roles, offering potential targets for pharmacologic intervention to prevent arterial thrombotic complications.
Area of Science:
- Cardiovascular Biology
- Vascular Inflammation
- Thrombosis Research
Background:
- Occlusive vascular disease commonly arises from thrombosis on atherosclerotic plaque.
- Plaque disruption exposes thrombogenic material, potentially causing vessel occlusion.
- Inflammation is central to atherosclerosis development and complications, influencing plaque stability.
Purpose of the Study:
- To elucidate the roles of inflammation and coagulation in atherosclerosis.
- To identify mechanisms underlying plaque evolution and thrombotic complications.
- To explore pharmacologic intervention points for reducing arterial thrombotic events.
Main Methods:
- Review of mechanisms in plaque formation and disruption.
- Analysis of inflammatory mediator roles in plaque cap composition.
- Investigation of coagulation factor influence on vascular cell functions.
Main Results:
- Inflammatory mediators regulate metalloproteinase and matrix production, affecting plaque cap integrity.
- Coagulation factors like thrombin influence vascular cell proliferation and cytokine release.
- Mural thrombi can integrate into plaques, promoting atherosclerotic lesion progression.
Conclusions:
- Atherosclerosis progression and thrombotic complications involve complex interactions between inflammation and coagulation.
- Targeting these mechanisms offers therapeutic opportunities to mitigate acute arterial thrombotic events.
Abstract:
Occlusive vascular disease most often results from thrombosis superimposed on atherosclerotic plaque. Disruption of plaque exposes thrombogenic substances within the plaque to blood and may result in thrombotic occlusion of the affected vessel. Mural thrombi may be incorporated into plaque, enhancing the evolution of atherosclerotic lesions. Inflammation plays a key role in the formation and complication of atherosclerosis. Inflammatory mediators regulate processes that determine the composition of the plaque's fibrous cap, a structure that separates blood from the thrombogenic lipid core. Several inflammatory mediators control the release of metalloproteinases (enzymes that break down cap constituents) from smooth muscle cells, macrophages and other cells within plaque. Inflammatory mediators also control the production of connective tissue matrix by cells in the plaque. Factors involved in coagulation, such as thrombin, can regulate non-thrombotic functions of vascular wall cells such as smooth muscle proliferation or cytokine release. The many mechanisms involved in arterial occlusive disease present numerous points at which intervention with pharmacologic agents may prove effective in lowering the risk of acute arterial thrombotic complications.