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ACE inhibition and atherogenesis
Bernward A Schölkens1, Wolfgang Landgraf
1Aventis Pharma Deutschland GmbH, Business Unit Cardiology/Thrombosis, Bad Soden, Germany. Bernward.Schoelkens@aventis.com
Insights
Angiotensin-converting enzyme (ACE) inhibitors reduce cardiovascular events by stabilizing atherosclerotic plaques. By inhibiting angiotensin II, these drugs decrease vascular inflammation and plaque rupture risk in high-risk patients.
Area of Science:
- Cardiovascular Medicine
- Pharmacology
- Vascular Biology
Background:
- Atherosclerosis is a chronic inflammatory vascular disease.
- Plaque rupture and thrombosis precipitate acute cardiovascular events.
- Endothelial dysfunction is a key feature driven by cardiovascular risk factors.
Purpose of the Study:
- To review the beneficial effects of ACE inhibitors on atherosclerosis.
- To elucidate the mechanisms by which ACE inhibitors impact plaque stability and thrombosis.
- To highlight the role of ACE inhibition in managing high-risk cardiovascular patients.
Main Methods:
- Review of clinical studies (HOPE, SECURE, APRES) and mechanistic insights.
- Analysis of the impact of ACE inhibitors on the renin-angiotensin system within the vascular wall.
- Examination of ACE inhibition's effects on endothelial function, inflammation, and plaque components.
Main Results:
- ACE inhibitors, like ramipril, improve prognosis in high-risk patients.
- Inhibition of angiotensin II formation protects endothelial function and reduces vascular inflammation.
- ACE inhibition decreases plaque instability by reducing inflammatory mediators and matrix metalloproteinases.
Conclusions:
- ACE inhibitors stabilize vulnerable atherosclerotic plaques by reducing local inflammation and ACE activity.
- This stabilization lessens the risk of plaque rupture, thrombosis, and subsequent cardiovascular events.
- ACE inhibition offers significant long-term prognostic benefits for patients with high cardiovascular risk.
Abstract:
Recent clinical studies such as HOPE, SECURE, and APRES show that angiotensin-converting enzyme (ACE) inhibitors like ramipril improve the prognosis of patients with a high risk of atherothrombotic cardiovascular events. Atherosclerosis, as a chronic inflammatory condition of the vascular system, can turn into an acute clinical event through the rupture of a vulnerable atherosclerotic plaque followed by thrombosis. ACE inhibition has a beneficial effect on the atherogenic setting and on fibrinolysis. Endothelial dysfunction is the end of a common process in which cardiovascular risk factors contribute to inflammation and atherogenesis. By inhibiting the formation of angiotensin II, ACE inhibitors prevent any damaging effects on endothelial function, vascular smooth muscle cells, and inflammatory vascular processes. An increase in the release of NO under ACE inhibition has a protective effect. Local renin-angiotensin systems in the tissue are involved in the inflammatory processes in the atherosclerotic plaque. Circulating ACE-containing monocytes, which adhere to endothelial cell lesions, differentiate within the vascular wall to ACE-containing macrophages or foam cells with increased local synthesis of ACE and angiotensin II. Within the vascular wall, angiotensin II decisively contributes to the instability of the plaque by stimulating growth factors, adhesion molecules, chemotactic proteins, cytokines, oxidized LDL, and matrix metalloproteinases. Suppression of the increased ACE activity within the plaque can lead to the stabilization and deactivation of the plaque by reducing inflammation in the vascular wall, thus lessening the risk of rupture and thrombosis and the resultant acute clinical cardiovascular events. The remarkable improvement in the long-term prognosis of atherosclerotic patients with increased cardiovascular risk might be the clinical result of the contribution made by ACE inhibition in the vascular wall.