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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.

Titel:	Essential role of protein kinase C βI in icariin-mediated protection against atherosclerosis.
Autor/in / Beteiligte Person:	Zhang, Y ; Xu, D ; Huang, P ; Li, Q ; Fan, Z ; Ren, L
Link:	Zum Volltext
Zeitschrift:	The Journal of pharmacy and pharmacology, Jg. 73 (2021-08-12), Heft 9, S. 1169-1179
Veröffentlichung:	2021- : [Oxford] : Oxford University Press ; <i>Original Publication</i>: London : Pharmaceutical Society of Great Britain, 2021
Medientyp:	academicJournal
ISSN:	2042-7158 (electronic)
DOI:	10.1093/jpp/rgab040
Schlagwort:	Animals Aorta metabolism Apolipoproteins E metabolism Cell Movement Cell Proliferation Cells, Cultured Cyclin D1 metabolism Humans Lipoproteins, LDL metabolism Matrix Metalloproteinase 9 metabolism Mice, Inbred C57BL Mice, Knockout Muscle, Smooth, Vascular cytology Muscle, Smooth, Vascular metabolism Muscle, Smooth, Vascular pathology Myocytes, Smooth Muscle drug effects Myocytes, Smooth Muscle metabolism Mice Aorta drug effects Atherosclerosis metabolism Epimedium chemistry Flavonoids pharmacology Muscle, Smooth, Vascular drug effects Plant Extracts pharmacology Protein Kinase C metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [J Pharm Pharmacol] 2021 Aug 12; Vol. 73 (9), pp. 1169-1179. MeSH Terms: Atherosclerosis* / metabolism ; Aorta / drug effects ; Epimedium / chemistry ; Flavonoids / pharmacology ; Muscle, Smooth, Vascular / drug effects ; Plant Extracts / pharmacology ; Protein Kinase C / metabolism ; Animals ; Aorta / metabolism ; Apolipoproteins E / metabolism ; Cell Movement ; Cell Proliferation ; Cells, Cultured ; Cyclin D1 / metabolism ; Humans ; Lipoproteins, LDL / metabolism ; Matrix Metalloproteinase 9 / metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular / cytology ; Muscle, Smooth, Vascular / metabolism ; Muscle, Smooth, Vascular / pathology ; Myocytes, Smooth Muscle / drug effects ; Myocytes, Smooth Muscle / metabolism ; Mice Grant Information: 81773934 National Natural Science Foundation of China Contributed Indexing: Keywords: PKC β; atherosclerosis; cell migration; cell proliferation; icariin; vascular smooth muscle cells Substance Nomenclature: 0 (Apolipoproteins E) ; 0 (Flavonoids) ; 0 (Lipoproteins, LDL) ; 0 (Plant Extracts) ; 0 (oxidized low density lipoprotein) ; 136601-57-5 (Cyclin D1) ; EC 2.7.11.13 (Protein Kinase C) ; EC 3.4.24.35 (Matrix Metalloproteinase 9) ; VNM47R2QSQ (icariin) Entry Date(s): Date Created: 20210406 Date Completed: 20220110 Latest Revision: 20240226 Update Code: 20240226

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Essential role of protein kinase C βI in icariin-mediated protection against atherosclerosis.