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Arya, Priyanka, Bhandari, Uma, Sharma, Kalicharan, Bansal, Priyanka. (1401). Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway. , 25(5), 577-585. doi: 10.22038/ijbms.2022.60467.13404
Priyanka Arya; Uma Bhandari; Kalicharan Sharma; Priyanka Bansal. "Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway". , 25, 5, 1401, 577-585. doi: 10.22038/ijbms.2022.60467.13404
Arya, Priyanka, Bhandari, Uma, Sharma, Kalicharan, Bansal, Priyanka. (1401). 'Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway', , 25(5), pp. 577-585. doi: 10.22038/ijbms.2022.60467.13404
Arya, Priyanka, Bhandari, Uma, Sharma, Kalicharan, Bansal, Priyanka. Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway. , 1401; 25(5): 577-585. doi: 10.22038/ijbms.2022.60467.13404

Anti-PCSK9 monoclonal antibody attenuates high-fat diet and zymosan-induced vascular inflammation in C57BL/6 mice by modulating TLR2/NF-ƙB signaling pathway

Iranian Journal of Basic Medical Sciences
مقاله 5، دوره 25، شماره 5، مرداد 2022، صفحه 577-585    اصل مقاله (835.86 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2022.60467.13404
نویسندگان
Priyanka Arya1؛ Uma Bhandari* 1؛ Kalicharan Sharma2؛ Priyanka Bansal1
1Department of Pharmacology, School of Pharmaceutical Education & Research (SPER), Jamia Hamdard, New Delhi - 110062, India
2Department of Pharmaceutical Chemistry, SPS, DPSRU, New Delhi-110017
چکیده
Objective(s): Excess intake of a high-fatty diet (HFD) together with zymosan administration mediates vasculitis response which leads to impaired serum lipid levels and causes arterial stiffness. In the development of new cholesterol-lowering medications, PCSK9 inhibitor (proprotein convertase subtilisin/kexin type 9) is an emerging therapeutic. The goal of the present study was to see whether anti-PCSK9 mAb1 might prevent vasculitis in C57BL/6 mice by blocking TLR2/NF-B activation in HFD and Zymosan-induced vasculitis. 
Materials and Methods: Protein-protein molecular docking was performed to validate the binding affinity of anti-PCSK9 mAb1 against TLR2. Under the experimental study, mice were randomly allocated to the following groups: Group I: standard mice diet (30 days) + Zymosan vehicle (sterile PBS solution of 5mg/ml on 8th day); Group II: HFD (30 days) + Zymosan ( single IP dose 80 mg/kg on day 8th); Group III: HFD+Zymosan + anti-PCSK9 mAb1 (6 mg/kg, s.c. on 10th and 20th days); Group IV: HFD+Zymosan+anti-PCSK9 mAb1 (10 mg/kg, s.c. on 10th and 20th days).
Results: In comparison with the low dose of anti-PCSK9 mAb1 (6 mg/kg), the high dose of anti-PCSK9 mAb1 (10 mg/kg) together with HFD and Zymosan inhibited vasculitis more effectively by decreasing aortic TLR2 and NF-B levels, reducing serum TNF- and IL-6, and up-regulating liver LDLR levels, which down-regulated serum LDL-C and improved serum lipids levels. Histopathological studies showed that anti-PCSK9 mAb1 treatment reduced plaque accumulation in the aorta of mice.
Conclusion: These findings indicate that anti-PCSK9 mAb1 has therapeutic potential in reducing HFD and Zymosan-induced vascular inflammation.  
کلیدواژه‌ها
Anti-PCSK9 antibody؛ High-fat diet؛ Inflammation؛ Toll-like receptor؛ Zymosan
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