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Effect of the anti-oxidant probucol on soluble thrombomodulin (sTM) in hypercholesterolemic rabbits
Introduction:
Thrombomodulin is an integral endothelial cell membrane protein, exists not only on the surface of endothelial cells but also as soluble fragments circulating in plasma. Probucol has anti-oxidant properties as well as cholesterol-lowering effects and may affect soluble thrombomodulin (sTM).
Methods:
Sixteen rabbits fed with high-cholesterol diet for 8 weeks were randomly divided into two groups: (1) high-cholesterol group (n=8): maintained high-cholesterol diet; (2) probucol group (n=8): the same diet plus probucol for 6 weeks. Control group (n=8) was fed with normal diet for 14 weeks. The levels of sTM and oxidized low-density lipoprotein (OX-LDL) were measured using ELISA.
Results:
There were atherosclerotic lesions in aortas and intimal thickness significantly increased in high-cholesterol group. Probucol significantly reduced the lesion area (56.4%+/-9.8% vs 82.5%+/-10.5%) and decreased the intimal thickness (44.65+/-7.25 mum vs 72.21+/-8.32) as compared with high-cholesterol group, all P<0.01. Probucol decreased the level of OX-LDL and sTM as compared with high-cholesterol group, all P<0.05.
Conclusions:
Probucol retarded the plaques formation may relate to decrease plasma OX-LDL and sTM concentration, which may improve endothelial function in hypercholesterolemic rabbit.
Insights
Probucol treatment significantly reduced atherosclerotic plaque formation and decreased oxidized low-density lipoprotein (OX-LDL) and soluble thrombomodulin (sTM) levels in hypercholesterolemic rabbits, suggesting improved endothelial function.
Area of Science:
- Cardiovascular Research
- Pharmacology
- Biochemistry
Background:
- Soluble thrombomodulin (sTM) is an endothelial cell marker, and its levels may be influenced by factors affecting endothelial function.
- Probucol, known for its antioxidant and cholesterol-lowering properties, has potential implications for cardiovascular health.
- This study investigates the effect of probucol on sTM and oxidized low-density lipoprotein (OX-LDL) in a rabbit model of hypercholesterolemia.
Discussion:
- Probucol administration significantly attenuated atherosclerotic lesion development and intimal thickening in rabbits fed a high-cholesterol diet.
- The probucol group exhibited reduced levels of plasma OX-LDL and sTM compared to the high-cholesterol group.
- These findings suggest that probucol's protective effects against atherosclerosis may be mediated by its impact on oxidative stress and endothelial markers.
Key Insights:
- Probucol effectively reduces atherosclerotic lesions and intimal hyperplasia in a hypercholesterolemic rabbit model.
- Probucol treatment leads to a significant decrease in plasma OX-LDL and sTM concentrations.
- The study highlights a potential link between probucol's anti-atherosclerotic effects and improvements in endothelial function.
Outlook:
- Further research could explore the precise molecular mechanisms by which probucol influences sTM and OX-LDL.
- Investigating the long-term efficacy and safety of probucol in preventing cardiovascular events is warranted.
- Translational studies may assess the potential of probucol or similar agents in managing hypercholesterolemia and related endothelial dysfunction in humans.
