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Angiotensin-converting enzyme expression in human carotid artery atherosclerosis
M Fukuhara1, R L Geary, D I Diz
1Hypertension and Vascular Disease Center, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Hypertension (Dallas, Tex. : 1979)
|January 21, 2000
Summary
This study found that angiotensin-converting enzyme (ACE) is present in human carotid artery plaques, particularly in inflammatory cells and microvessels. Increased ACE production in these areas may drive atherosclerosis progression.
Area of Science:
- Cardiovascular Biology
- Vascular Pathology
- Molecular Medicine
Background:
- Angiotensin-converting enzyme (ACE) inhibitors show promise in animal models of atherosclerosis and human myocardial infarction.
- While ACE components are found in coronary arteries, their presence in carotid arteries, a common atherosclerosis site, is unknown.
- Carotid artery atherosclerosis is a significant cause of stroke.
Purpose of the Study:
- To investigate the presence and localization of ACE mRNA and protein in human carotid atheromatous lesions.
- To determine if ACE expression is associated with specific cell types within atherosclerotic plaques.
- To understand the role of ACE in carotid artery plaque progression.
Main Methods:
- Analysis of 24 human carotid endarterectomy specimens with advanced atherosclerotic lesions (Stary type V and VI).
- Localization of ACE mRNA and protein using in situ hybridization and immunohistochemistry.
- Colocalization of ACE with cell-specific markers (smooth muscle cells, endothelial cells, macrophages, lymphocytes).
Main Results:
- ACE protein and mRNA were detected in the intima of carotid plaques, primarily within macrophages and microvessels.
- ACE expression was significantly higher in macrophage-rich areas and plaque shoulder regions.
- Microvessel ACE expression was associated with inflammation; smooth muscle cells showed minimal ACE staining.
Conclusions:
- Atherosclerosis alters ACE production in the carotid artery, with increased transcription and translation in inflamed plaque regions.
- Inflammation-driven ACE expression in carotid plaques may contribute to the progression of atherosclerosis.
- These findings highlight a potential mechanism linking inflammation and ACE in vascular disease.