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Plaque disruption and thrombosis: potential role of inflammation and infection
1Division of Cardiology and the Atherosclerosis Research Center, Room 5347, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. Shahp@chs.org
Insights
Acute coronary syndromes arise from plaque disruption and thrombosis. Inflammation plays a key role in plaque instability and clot formation, offering targets for new treatments.
Area of Science:
- Cardiovascular Medicine
- Pathology
- Immunology
Background:
- Acute coronary syndromes (ACS) stem from coronary thrombosis on atherosclerotic plaques.
- Plaque disruption, via rupture or erosion, initiates thrombosis.
- Many ACS cases originate from non-obstructive plaques.
Purpose of the Study:
- To elucidate the role of inflammation in atherosclerotic plaque disruption and thrombosis.
- To identify mechanisms linking inflammation to plaque instability and ACS development.
Main Methods:
- Review of current literature on atherosclerotic plaque pathophysiology.
- Analysis of inflammatory mediators and cellular processes involved in plaque rupture/erosion.
- Examination of the link between inflammation and thrombosis in ACS.
Main Results:
- Inflammation, involving mononuclear cells and proteases, contributes to plaque destabilization and smooth muscle cell apoptosis.
- Inflammatory processes can promote thrombosis by providing tissue factor.
- Modified lipids, stress, and infections (e.g., Chlamydia pneumoniae) can trigger plaque inflammation.
Conclusions:
- Inflammation is a critical factor in the pathophysiology of atherosclerotic plaque disruption and thrombosis.
- Understanding these inflammatory pathways may lead to novel strategies for stabilizing atherosclerotic disease and preventing ACS.
Abstract:
Acute coronary syndromes (unstable angina, acute myocardial infarction, and ischemic sudden death) result from coronary thrombosis superimposed on an atherosclerotic plaque. Thrombosis is generally a consequence of disruption of the atherosclerotic plaque in the form of a fissure/rupture in the fibrous cap overlying a lipid-rich pool or superficial endothelial erosion covering a smooth muscle and proteoglycan-rich matrix with or without a lipid-core. Approximately 2/3 of acute coronary syndromes evolve from atherosclerotic plaques that are minimally or mildly obstructive of the lumen before the acute event. Inflammation with accumulation of activated mononuclear cells may play a potential role in plaque disruption through the elaboration of proteases, such as matrix degrading neutral metalloproteinases and other proteases, inhibition of function and/or survival, or promotion of apoptosis of matrix synthesizing smooth muscle cells. Inflammation may also contribute to thrombosis after plaque disruption by providing a source for tissue factor in the plaque. Inflammation in the plaque may result from accumulation of modified lipids, oxidant and hemodynamic stress, and infectious agents, such as Chlamydia pneumoniae or pro-inflammatory triggers from distant sites of infection and inflammation (eg, chronic gingivitis and chronic bronchitis). Improved insights into the pathophysiology of plaque disruption and thrombosis are likely to provide new and improved methods of stabilizing atherosclerotic disease process.