IMR Press / FBL / Volume 26 / Issue 6 / DOI: 10.52586/4929
Open Access Original Research
AGEs promote calcification of HASMCs by mediating Pi3k/AKT-GSK3𝜷 signaling
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1 Department of General Surgery (Vascular Surgery), The Affiliated Hospital of Southwest Medical University, 646000 Luzhou, China
2 Department of Pediatric Surgery & Vascular Surgery, Zigong Fourth People’s Hospital, 643000 Zigong, China
3 Department of Vascular Surgery, Southwestern Medical University Affiliated Chinese Medicine Hospital, 646000 Luzhou, China
4 Cardiovascular and Metabolic Diseases Key Laboratory of Luzhou, 646000 Luzhou, China
5 Key Laboratory of Medical Electrophysiology, Ministry of Education & Medical Electrophysiological Key Laboratory of Sichuan Province, (Collaborative Innovation Center for Prevention of Cardiovascular Diseases) Institute of Cardiovascular Research, Southwest Medical University, 646000 Luzhou, China
*Correspondence: (Yong Liu)
Front. Biosci. (Landmark Ed) 2021, 26(6), 125–134;
Submitted: 11 September 2020 | Accepted: 5 March 2021 | Published: 30 May 2021
Copyright: © 2021 The Author(s). Published by BRI.
This is an open access article under the CC BY 4.0 license (

This study aimed to investigate the effects of advanced glycation end products (AGEs) on the calcification of human arterial smooth muscle cells (HASMCs) and to explore whether AGEs can promote the calcification of HASMCs by activating the phosphoinositide 3-kinase (PI3K)/AKT-glycogen synthase kinase 3 beta (GSK3-β) axis. Cultured HASMCs were divided into five groups: blank control group, dimethyl sulfoxide (vehicle) group, AGEs group, LY294002 (AKT inhibitor) group, and TWS119 (GSK3-β inhibitor) group. Cells were pretreated with either vehicle, LY294002, or TWS119 for 2 hours followed by incubation with AGEs (25 μg/mL) for 5 days, and the expression levels of proteins in each group were analyzed by western blotting. AGE treatment promoted HASMC calcification, which coincided with increased expression of p-AKT and p-GSK3-β (serine 9). Also, AGEs upregulated the expression of osteoprotegerin and bone morphogenetic protein, and these effects were suppressed by LY294002 but enhanced by TWS119. In conclusion, AGEs promote calcification of HASMCs, and this effect is ameliorated by inhibition of AKT activity but potentiated by inhibition of GSK3-β activity. Hence, AGEs trigger HASMC calcification by regulating PI3K/AKT-GSK3-β signaling.

Advanced glycation end products
Fig. 1.
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