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ABCA1 expression in carotid atherosclerotic plaques
C Albrecht1, S Soumian, J S Amey
1MRC Clinical Sciences Centre, Faculty of Medicine, Imperial College, Hammersmith Hospital, Du Cane Road, London, UK.
Stroke
|November 6, 2004
Summary
Reduced ATP-binding cassette transporter A1 (ABCA1) protein, despite increased mRNA, is found in advanced atherosclerotic lesions. This suggests local plaque factors, not systemic levels, may drive atherosclerosis development.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- ATP-binding cassette transporter A1 (ABCA1) is crucial for cellular cholesterol efflux and reverse cholesterol transport.
- Previous research primarily investigated ABCA1 mutations; this study examines ABCA1's role in human carotid atherosclerosis.
Purpose of the Study:
- To investigate the role of ABCA1 in human carotid atherosclerotic disease.
- To compare ABCA1 and liver X receptor alpha (LXRalpha) expression in atherosclerotic versus healthy arterial tissue.
Main Methods:
- Quantitative real-time PCR measured ABCA1 and LXRalpha mRNA in 18 atherosclerotic and 10 control carotid artery specimens.
- Immunoblotting assessed ABCA1 protein levels in arterial tissue.
- Leukocyte ABCA1 mRNA was measured in patients undergoing carotid endarterectomy and controls.
Main Results:
- ABCA1 and LXRalpha mRNA levels were significantly elevated in atherosclerotic plaques.
- ABCA1 protein expression was markedly reduced in atherosclerotic plaques compared to controls.
- Leukocyte ABCA1 mRNA levels showed no significant difference between groups.
Conclusions:
- Despite elevated ABCA1 mRNA, likely mediated by LXRalpha, ABCA1 protein is reduced in advanced carotid atherosclerotic lesions.
- The plaque microenvironment appears to influence ABCA1 expression, leading to decreased protein levels.
- Reduced ABCA1 protein is proposed as a key factor in atherosclerotic lesion development.