Defibrotide's activity on leukocytes and platelets in rabbits with diet-induced atherosclerosis

Area of Science:

• Cardiovascular Science
• Pharmacology

Background:

• Atherosclerosis is a chronic inflammatory disease characterized by plaque buildup in arteries.
• Elevated cholesterol levels are a significant risk factor for atherosclerosis progression.
• Leukocytes and platelets play crucial roles in the inflammatory and thrombotic processes of atherosclerosis.

Purpose of the Study:

• To investigate the effects of oral Defibrotide on atherosclerosis markers in a cholesterol-fed model.
• To evaluate Defibrotide's impact on leukocyte and platelet counts and vascular inflammation.
• To determine Defibrotide's efficacy in reducing atherosclerotic lesion area and intimal thickening.

Main Methods:

• Administration of oral Defibrotide to a cholesterol-diet induced atherosclerosis model.
• Quantification of leukocyte and platelet counts.
• Assessment of the atherosclerotic lesion area in the aorta.
• Histopathological analysis to determine the frequency of intimal thickening in kidney, heart, and cardiac valves.

Main Results:

• Oral Defibrotide significantly decreased leukocyte and platelet counts.
• Defibrotide reduced the percentage of aorta endothelial surface involved in atherosclerosis.
• A notable reduction in intimal thickening was observed in the blood vessels of kidneys (47%), hearts (29%), and cardiac valves (17%).

Conclusions:

• Oral Defibrotide demonstrates a therapeutic effect in mitigating atherosclerosis.
• Defibrotide appears to act by modulating leukocyte and platelet activity and numbers.
• The findings suggest Defibrotide's potential as a treatment to reduce atherosclerotic burden and vascular complications.