Tetrandrine ameliorated atherosclerosis in vitamin D3/high cholesterol diet-challenged rats via modulation of miR-34a and Wnt5a/Ror2/ABCA1/NF-kB trajectory

Abstract

Abstract Atherosclerosis (AS) is a major cause of cardiovascular diseases that may lead to mortality. This study aimed to evaluate the therapeutic potential of tetrandrine in high cholesterol diet (HCD)-induced atherosclerosis, in rats, via modulation of miR-34a, as well as, Wnt5a/Ror2/ABCA1/NF-κB pathway and to compare its efficacy with atorvastatin. Induction of AS, in male rats, was done via IP administration of vitamin D3 (70 U/Kg for 3 days) together with HCD. At the end of the 9th week, rats were treated with atorvastatin at a dose of 20 mg/kg, and tetrandrine at different doses of (18.75, and 31.25 mg/kg) for 22 days. Serum inflammatory cytokines and lipid profile, liver oxidative stress parameters, and aortic tissue Wnt5a, Ror2, ABCA1, NF-κB, miR-34a levels were assessed in all experimental groups. Histopathological and Immunohistochemical assessments of aortic tissue sections were done. Results showed that tetrandrine treatment reverted the inflammatory and oxidative stress state together with reducing the serum lipids via modulating miR-34a, and Wnt5a/Ror2/ABCA1/NF-κB pathway. Moreover, it reverted the histopathological abnormalities observed in AS rats. Tetrandrine beneficial effects, in both doses, were comparable to that of atorvastatin, in most of the discussed parameters. These findings praise tetrandrine as a promising agent for management of atherosclerosis.

Keywords

• HCD (high cholesterol diet)
• AS (atherosclerosis)
• Tetrandrine
• Wnt5a/Ror2/ABCA1/NF-κB pathway
• miR-34