The role of cholesterol-enriched diet and paraoxonase 1 inhibition in atherosclerosis progression

Introduction: Atherosclerosis could be deemed as a chronic, progressive, and inflammatory disease. It has been well-documented that high-density lipoprotein (HDL) can reduce the risk of the atherosclerosis occurrence through exerting some anti-atherogenic mechanisms. In recent years, the strong evidence has suggested that paraoxonase 1 (PON1) may contribute to antioxidant properties of HDL. In the present study, the impact of a diet enriched with cholesterol and also the PON1 inhibition on atheroma formation and lipid profile has been investigated. Methods: In this study, 24 New Zealand rabbits were randomly assigned to three groups receiving standard diet, atherogenic diet, and atherogenic diet plus once daily intramuscular injection of nandrolone decanoate as the PON1 inhibitor. Triglyceride, cholesterol, HDL, and low-density lipoprotein (LDL) were determined and both cholesterol accumulation in aorta and fatty streak formation were evaluated. Results: The comparison of the results in three groups reveals that cholesterol level in the group received cholesterol-enriched diet plus once daily injection of PON1 inhibitor was higher than the groups received standard diet or atherogenic diet without PON1 inhibitor (P < 0.05). Furthermore, the percentage of atheroma with type-I lesions was equal to 75% compared with the group received atherogenic diet plus nandrolone at 30%. Additionally, the differences in fatty streak formation in aorta, as well as the right and left coronary arteries in three groups given show that the difference between groups receiving atherogenic diet and standard diet was significantly lower (P < 0.05) than the difference between groups receiving atherogenic diet plus PON1 inhibitor and standard diet. Conclusion: It can be concluded that lack of paraoxanase1 or even reduced the activity of this enzyme could accelerate the progression of fatty streak lesions toward advanced atherosclerotic lesions.