Related Experiment Video
Updated: Aug 16, 2026
Differential Effects of Lipid-lowering Drugs in Modulating Morphology of Cholesterol Particles
Published on: November 10, 2017
Modulating effects of cholesterol feeding and simvastatin treatment on platelet-activating factor acetylhydrolase
Bo Zhang1, Ping Fan, Eiso Shimoji
1Department of Cardiology, Fukuoka University School of Medicine, 7-45-1 Nanakuma Jonan-ku, Fukuoka 814-0180, Japan.
Insights
Cholesterol feeding increases platelet-activating factor acetylhydrolase (PAF-AH) activity, while simvastatin treatment decreases it, affecting coronary heart disease risk factors.
Area of Science:
- Biochemistry
- Cardiovascular Science
- Pharmacology
Background:
- Platelet-activating factor acetylhydrolase (PAF-AH) degrades PAF and oxidized lipids.
- Elevated PAF-AH is a risk factor for coronary heart disease.
- Investigating PAF-AH modulation by cholesterol and statins is crucial for cardiovascular health.
Purpose of the Study:
- To examine the effects of cholesterol feeding and simvastatin on plasma PAF-AH activity.
- To understand the mechanisms underlying these modulations.
Main Methods:
- Rabbits were fed a cholesterol-rich diet for 1 month.
- Subsequent treatment involved simvastatin administration for 2 months.
- Lipoprotein subfractions, lipid levels, and PAF-AH activity were analyzed.
Main Results:
- Cholesterol feeding increased plasma PAF-AH activity and LDL-associated PAF-AH (LDL-PAF-AH) activity.
- Simvastatin treatment decreased plasma and LDL-PAF-AH activities.
- Cholesterol increased PAF-AH secretion from macrophages; simvastatin did not affect secretion but enhanced LDL particle clearance.
Conclusions:
- Cholesterol elevation and simvastatin-induced cholesterol lowering modulate plasma PAF-AH activity through distinct mechanisms.
- These findings provide insights into the role of PAF-AH in cardiovascular disease and statin therapy.
Background:
Platelet-activating factor acetylhydrolyse (PAF-AH) is an enzyme that degrades PAF and bioactive oxidized lipids. However, it has been reported to be a risk factor for coronary heart disease. The present study examined the effects of cholesterol feeding and simvastatin treatment on plasma PAF-AH activity.
Methods:
Japanese White rabbits (n=22) were fed a diet containing 0.3% cholesterol and 3% corn oil for 1 month, and then divided into two groups that continued to receive this diet with (treated) or without (control) treatment with simvastatin (0.01%) for another 2 months.
Results:
Cholesterol feeding increased and simvastatin treatment decreased apolipoprotein (apo) B-containing lipoprotein subfractions as characterized by capillary isotachophoresis, serum levels of total cholesterol, phospholipids, LDL-C, apoE, plasma and LDL-associated PAF-AH (LDL-PAF-AH) activities, and plasma lyso-PC concentration. Cholesterol feeding also increased apoB levels but decreased the LDL-PAF-AH/LDL-C ratio and did not change the plasma PAF-AH/lyso-PC ratio. Simvastatin treatment did not affect apoB levels and only slightly increased the LDL-PAF-AH/LDL-C ratio. Secretion of PAF-AH activity from monocyte-derived macrophages was increased by cholesterol feeding but not affected by simvastatin treatment. These results indicate that PAF-AH activity is increased by cholesterol feeding due to increased secretion of PAF-AH activity from macrophages and that PAF-AH activity is decreased by simvastatin due to increased removal of lipid and enzyme contents of LDL particles.
Conclusion:
Cholesterol elevation by cholesterol feeding and cholesterol-lowering by simvastatin modulate plasma PAF-AH activity by different mechanisms.
Related Concept Videos
01:20Lipid-Lowering Drugs: Statins and Miscellaneous Agents
01:29Cholesterol: Significance and Regulation
Considering cholesterol and...