The effect of evolocumab alone and in combination with atorvastatin on atherosclerosis progression and TLRs expression.

Evolocumab, a PCSK-9 inhibitor, is known for its ability to reduce low-density lipoprotein cholesterol (LDL-C). This study aimed to investigate the effects of evolocumab, alone or in combination with atorvastatin, on the progression of atherosclerosis. Fifty male domestic rabbits were randomly assigned to five groups: control, high cholesterol diet, evolocumab vehicle (dimethyl sulfoxide, DMSO), evolocumab alone, and evolocumab plus atorvastatin. Serum levels of interleukin 10 (IL-10), IL-17, IL-1ß, intracellular adhesion molecule (ICAM), and vascular adhesion molecule (VCAM) were measured. Toll-like receptor (TLR) expression on monocytes was evaluated using flow cytometry. Histopathological examination and measurement of intimal thickness (IT) were also conducted. The results revealed that the evolocumab produced a statistically significant (p<0.05) reduction in lipid profile at 5 weeks, with the peak effect occurring at 10 weeks. Furthermore, the inhibitor reduced TLRs at 10 weeks to 10.83±1.8 and intimal thickness to 160.66±9.45. IL-17, IL-1ß, ICAM, and VCAM were significantly reduced by evolocumab treatment, with the improvement of the histopathological changes in the aortic wall. The combination of evolocumab and atorvastatin caused a more statistically significant reduction in TLRs at 10 weeks to 5.08±1.2 and intimal thickness to 121.79±5.3. IL-17, IL-1ß, ICAM, and VCAM were significantly (p<0.05) reduced by the combination, and the histopathological changes in the aortic wall were significantly improved. In conclusion, evolocumab delays the progression of atherosclerosis by modulating inflammatory pathways.

THE EFFECT OF EVOLOCUMAB ALONE AND IN COMBINATION WITH ATORVASTATIN ON LIPID PROFILE.

OBJECTIVE: The aim: In this study, we try to investigate whether evolocumab or its combination with atorvastatin has potent effect on lipid profile? PATIENTS AND METHODS: Materials and methods: Forty local domestic male rabbits were included in this study, and categorized into four group, two untreated group (nohypercholostermic and untreated hypercholostermic) and treated groups (evolocumab treated group at dose 6.1mg/kg/2Wk and atorvastatin treated group at dose 3.5 mg/kg/day),the blood samples were analyzed at base line and after 5week and at the end of the study after 10 weeks for lipid profile by standard enzymatic methods. RESULTS: Results: The serum levels of total cholesterol, triglyceride, low-density lipoprotein cholesterol (LDL-C),were increased after 10 weeks of administration of the atherogenic diet significantly (p<0.05) as compared with other groups (group I: 61.19 ± 14, group ΙΙ: 1301 ± 443, group ΙΙΙ 41.01 ± 5.81: 280 ± 50, group ΙV: 190 ± 38 group Ι: 46 ± 15.0, group ΙΙ: 256.0 ± 24.0, group ΙΙΙ: 101.0±28, group ΙV: 48.18 ± 15.27, group Ι: 29±14.50, group ΙΙ: 929±251.0, group ΙΙΙ: 283.0±36, group ΙV: 209.0±33mg/dl) respectively while the levels of high-density lipoprotein cholesterol (HDL-C) decrease (18.0±4.1 to 15.0±3.0mg/dl). Compared with evolocumab monotherapy, combination of evolocumab and atorvastatin reduce serum level of total cholesterol, triglyceride and low density lipoprotein more than that of evolocumab. CONCLUSION: Conclusions: Preproteins convert as esubtilisin/kexin type 9 inhibitor regulates the serum levels of lipid and cholesterol by lowering LDL-C, and the results also indicate that combination of evolocumab and atorvastatin are more potent in lowering the lipid profile and then reduce progression of atherosclerosis than evolocumab alone in rabbits suggesting that this combination might be beneficial for treatment of atherosclerosis.