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Effects of reducing LDL and increasing HDL with gemfibrozil in experimental coronary lesion development and
C P Palazón1, J Alfón, P Gaffney
1Cardiovascular Research Center, CSIC-HSCSP-UAB, Barcelona, Spain.
Insights
Gemfibrozil effectively lowers LDL cholesterol and raises HDL cholesterol in pigs fed a high-cholesterol diet. This lipid-lowering drug also reduced vascular lesions and fibrin formation without increasing platelet activation.
Area of Science:
- Cardiovascular Disease Research
- Pharmacology
- Atherosclerosis Studies
Background:
- Lipid-lowering drugs aid cardiovascular disease prevention.
- Gemfibrozil shows lipid-lowering benefits but may activate platelets in vitro.
- Porcine models are valuable for studying atherosclerosis and lipid-lowering interventions.
Purpose of the Study:
- To evaluate gemfibrozil's efficacy in preventing early vascular effects of a cholesterol-rich diet in pigs.
- To determine if gemfibrozil induces platelet activation and mural thrombosis.
- To assess gemfibrozil's impact on vascular lesions, platelet deposition, and fibrin formation.
Main Methods:
- Pigs were fed a diet high in saturated fat and cholesterol for 50 days.
- Gemfibrozil was administered, maintaining average therapeutic plasma levels.
- Vascular effects, lipid profiles, fibrinogen levels, platelet deposition, and lesion severity were analyzed.
Main Results:
- Gemfibrozil significantly reduced LDL cholesterol and increased HDL cholesterol.
- The drug prevented the diet-induced increase in plasma fibrinogen levels.
- Vascular lesions were less severe in gemfibrozil-treated pigs, with reduced fibrin deposition and unchanged platelet deposition.
Conclusions:
- Gemfibrozil effectively lowers lipids and slows atherosclerosis progression in a porcine model.
- The intervention reduced fibrin formation on damaged vessel walls without promoting platelet mural thrombosis.
- Gemfibrozil represents a potential therapeutic strategy for managing atherosclerosis by modulating lipid levels and vascular inflammation.
Abstract:
The use of lipid-lowering drugs has been shown to have beneficial effects in primary and secondary prevention of cardiovascular disease. Gemfibrozil has shown beneficial effects as a lipid lowering agent; however, some proactivating effects on platelet function in vitro have been described. We have studied in a porcine model of atherosclerosis if gemfibrozil could prevent the early vascular effects of a cholesterol-rich diet without inducing platelet activation and, hence, mural thrombosis. Pigs were fed for 50 days with a diet rich in saturated fat and cholesterol (cho). The longitudinal follow-up study showed that in control animals LDL-cho increased significantly up to 181.9 +/- 34.2 mg/dl or 79% of total-cho, while HDL-cho was reduced to 19% of total-cho. Gemfibrozil, at average therapeutic plasma levels (peak levels of 28 micrograms/ml) [corrected], induced a significant reduction in the relative amount of LDL (P < 0.05) and increased HDL (P < 0.05). The increase in fibrinogen plasma levels observed in the control group due to the dietary intervention (+25%) was prevented in the treated animals (-5%). In treated animals, vascular lesions were significantly less severe, platelet deposition upon exposure of damaged vessel wall was unchanged and the fibrin layer deposited on the damaged vessel wall was significantly reduced over control animal values. This short term pharmacologic lipid lowering intervention has been able to slow down lesion development and to reduce fibrin formation onto lesioned disrupted vascular substrates without increasing platelet mural thrombosis.