Opposite pattern of MDR1 and caveolin-1 gene expression in human atherosclerotic lesions and proliferating human smooth muscle cells
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Updated: Aug 6, 2026
Calcification of Vascular Smooth Muscle Cells and Imaging of Aortic Calcification and Inflammation
Published on: May 31, 2016
B Batetta1, M F Mulas, P Petruzzo
1Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di Cagliari, Italy.
Abstract:
Cholesterol esterification and smooth muscle cell (SMC) proliferation are the crucial events in the development of atherosclerotic lesions. The objective of this study was to analyse cholesterol esterification and the expression of MDR1 (multidrug resistance), ACAT (acyl-CoA:cholesterol acyltransferase) and caveolin-1 genes in atherosclerotic and healthy vascular walls, in SMCs obtained from atherosclerotic lesions and saphenous veins. Results demonstrated higher levels of cholesterol esters, ACAT and MDR1 mRNAs and lower levels of caveolin-1 mRNA in atherosclerotic segments compared to adjacent serial sections of the same artery and the corresponding non-atherosclerotic arteries from cadaveric donors. SMCs isolated from atherosclerotic plaques manifested an increased capacity to esterify cholesterol and to grow at a faster rate than SMCs isolated from saphenous veins. In addition, when SMCs from atherosclerotic plaques were cultured in the presence of progesterone, a potent inhibitor of cholesterol esterification, significant growth suppression was observed. An increase in ACAT and MDR1 expression and a concomitant decrease in caveolin-1 expression were also observed in SMCs isolated from atherosclerotic arteries as early as 12 h after serum stimulation. An opposite pattern was found when SMCs were treated with progesterone. These findings support the idea that cholesterol esterification plays a role both in early atherogenesis and in clinical progression of advanced lesions and raise the possibility that the cholesterol ester pathway might directly modulate the proliferation of SMCs.
Insights
Cholesterol esterification drives atherosclerosis by increasing smooth muscle cell proliferation. Inhibiting this process, via ACAT and MDR1 gene expression, suppressed SMC growth, suggesting a therapeutic target for cardiovascular disease.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Atherosclerosis Research
Background:
- Cholesterol esterification and smooth muscle cell (SMC) proliferation are key in atherosclerotic lesion development.
- Understanding the molecular mechanisms governing these processes is crucial for therapeutic intervention.
Purpose of the Study:
- To investigate cholesterol esterification and gene expression (MDR1, ACAT, caveolin-1) in atherosclerotic vs. healthy vascular tissue.
- To analyze cholesterol esterification and proliferation in SMCs from atherosclerotic plaques and saphenous veins.
Main Methods:
- Comparative analysis of gene expression (mRNA) in vascular segments.
- Isolation and culture of SMCs from atherosclerotic plaques and saphenous veins.
- Assessment of cholesterol esterification capacity and proliferation rates.
- Inhibition studies using progesterone, a cholesterol esterification inhibitor.
Main Results:
- Atherosclerotic segments showed higher cholesterol esters, ACAT, and MDR1 mRNA, with lower caveolin-1 mRNA compared to healthy controls.
- SMCs from atherosclerotic plaques exhibited increased cholesterol esterification and proliferation.
- Progesterone treatment significantly suppressed SMC growth from atherosclerotic plaques.
- Serum stimulation of atherosclerotic SMCs increased ACAT/MDR1 and decreased caveolin-1 expression within 12 hours.
Conclusions:
- Cholesterol esterification is implicated in both early atherogenesis and advanced lesion progression.
- The cholesterol ester pathway appears to directly modulate SMC proliferation.
- Targeting cholesterol esterification pathways presents a potential therapeutic strategy for atherosclerosis.
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