Essential role of protein kinase C betaI in icariin-mediated protection against atherosclerosis
J Pharm Pharmacol. 2021 Aug 12;73(9):1169-1179. doi: 10.1093/jpp/rgab040.
ABSTRACT
OBJECTIVES: This study aimed to clarify the superior beneficial effects of icariin on atherosclerosis, as well as to explore the possible underlying mechanisms for its effect via the modulation of protein kinase C βI.
METHODS: Lipid profiles were determined while dissected aortas were prepared of ApoE-/- mice. The expression of protein kinase C βI and phosphorylation of protein kinase C βI were determined by immunohistochemistry analysis. Human vascular smooth muscle cells were subjected to ox-LDL stimulation. MTS assay was conducted to detect cell proliferation. A transwell migration assay was performed to evaluate migration capacity. Flow cytometric analysis was used to determine cell cycle progression. Quantitative real-time PCR and western blot were performed to assess gene expression.
RESULTS: Icariin significantly alleviated atherogenesis, as well as protein levels of protein kinase C βI and phosphorylated protein kinase C βI in the aorta. Icariin effectively suppressed cell proliferation and migration. protein kinase C βI, cyclin D1 and matrix metalloproteinase-9 were modulated in response to treatment with icariin. Protein kinase C activator reversed the protective effect of icariin on human vascular smooth muscle cells against ox- low-density lipoprotein, protein kinase C β inhibitor augmented the inhibitory effect of icariin.
CONCLUSIONS: Our findings highlight the probable application of icariin in atherosclerotic therapy and reveal that protein kinase C βI acts as a crucial regulator in the anti-atherosclerotic action of icariin.
PMID:33822184 | DOI:10.1093/jpp/rgab040