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Pathogenetic concepts of acute coronary syndromes
Roberto Corti1, Valentin Fuster, Juan Jose Badimon
1Zena and Michael A. Wiener Cardiovascular Institute, The Mount Sinai School of Medicine, New York, New York 10029, USA
Insights
Plaque vulnerability, not just stenosis, drives ischemic events. Inflammation and endothelial dysfunction promote atherothrombosis, increasing risk.
Area of Science:
- Cardiovascular Biology
- Pathophysiology of Atherothrombosis
Background:
- Plaque rupture is a primary cause of ischemic events.
- Atherosclerosis and thrombosis are interconnected processes, termed atherothrombosis.
- Plaque vulnerability, influenced by composition and inflammation, is key, not just stenosis.
Purpose of the Study:
- To explore the mechanisms underlying plaque disruption and atherothrombosis.
- To highlight the roles of inflammation and endothelial dysfunction in thrombotic complications.
Main Methods:
- Review of current understanding of plaque biology and thrombotic processes.
- Analysis of the interplay between atherosclerotic plaque characteristics and thrombus formation.
- Examination of the endothelial cell's role in vascular homeostasis and hemostasis.
Main Results:
- Plaque composition and inflammation (monocyte/macrophage activation) significantly determine plaque vulnerability and thrombogenicity.
- Superficial erosion of fibrotic plaques can cause acute coronary syndromes, exacerbated by hypercoagulable states.
- Endothelial dysfunction, induced by risk factors, impairs nitric oxide bioavailability and promotes a pro-thrombotic state.
Conclusions:
- Atherothrombosis involves complex interactions between plaque instability, inflammation, and the vascular endothelium.
- Endothelial dysfunction is central to maintaining hemostasis and preventing thrombotic complications.
- Understanding these mechanisms is crucial for managing ischemic events and cardiovascular disease.
Abstract:
The propensity of plaque to disrupt is a major determinant of future ischemic events. Although they are distinct from one another, the atherosclerotic and thrombotic processes appear to be interdependent and may be integrated under the term "atherothrombosis." It is now clear that plaque composition, rather than the percent stenosis, is a major determinant of plaque vulnerability. Plaque disruption seems to depend on both passive and active phenomena and is not purely mechanical. Inflammation (activation of monocytes/macrophages) is a major determinant of both plaque vulnerability and thrombogenicity as they relate to plaque disruption. In one-third of acute coronary syndromes, there is, however, no plaque disruption but only superficial erosion of a markedly stenotic, fibrotic plaque. In these cases, thrombus formation may be exacerbated by a hyperthrombogenic state present in patients with certain systemic risk factors. The endothelium plays a pivotal role in vascular homeostasis and hemostasis. This dynamic organ regulates blood thrombogenicity as well as contractile, secretory, and mitogenic activities in the vessel wall. Some classic risk factors induce endothelial dysfunction by reducing the bioavailability of nitric oxide, increasing tissue endothelin-1, and activating pro-inflammatory signaling pathways. Vascular hemostasis, which is the maintenance of blood fluidity and vascular integrity, is achieved by counter-balancing the intrinsic clotting tendency of blood. As a consequence of the central role of endothelial cells in hemostatic control, a dysfunctional endothelium will generate a pro-thrombotic environment favoring development of atherosclerotic lesions and thrombotic complications.