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

Abstract

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.

Paraoxonase 1 and atherosclerosis

“…It is susceptible both to atherosclerosis induced nutritionally and by apoE deficiency ( 35 ). Consistent with this, rabbits fed an atherogenic diet developed more advanced atherosclerotic lesions when PON1 activity was inhibited with nandrolone ( 94 ). As long ago as 2002 a US patent was registered ( 95 ) for the prevention of atherosclerosis by injection of a preparation of PON1 192Q isoform based on a mouse model.…”

N1‐methylnicotinamide (MNAM) as a guardian of cardiovascular system

“…A growing body of evidence indicates that lipid and fatty acid (FA) metabolism play a pivotal role in cardiovascular physiopathology (Amani et al, ; Darabi et al, ; Noori et al, ; Paytakhti et al, ; Pezeshkian et al, , ). LDs are cellular organelles, which act as fat depots (Walther & Farese, ).…”

Prolonged High-Fat Diet Feeding of WHHLMI Rabbits does Not Aggravate Metabolic or Cardiac Dysfunction

“…The reason why the HFD did not accelerate atherogenesis and subsequent development of MI might be multifactorial. To stimulate atherogenesis, experimental diets enriched in cholesterol are used [15][16][17] . Our 57T4 diet was enriched with 32 ppm (or 0.003%) cholesterol, while the SFD (5322 diet) was devoid of cholesterol.…”

“…Our 57T4 diet was enriched with 32 ppm (or 0.003%) cholesterol, while the SFD (5322 diet) was devoid of cholesterol. Most atherogenic diets are enriched with 0.015 % up to 2% cholesterol [15][16][17] and therefore the lower amount of cholesterol in our diet may partially explain the lack of atheroma progression. Exposing rabbits for one year to a HFD would expected to be long enough to aggravate atherogenesis in a model of familial hypercholesterolemia.…”