Abstract
Excessive production and migration of vascular smooth muscle cells (VSMCs) are associated with vascular remodeling that causes vascular diseases, such as restenosis and hypertension. Angiotensin II (Ang II) stimulation is a key factor in inducing abnormal VSMC function. This study aimed to investigate the effects of 6′-sialyllactose (6′SL), a human milk oligosaccharide, on Ang II-stimulated cell proliferation, migration and osteogenic switching in rat aortic smooth muscle cells (RASMCs) and human aortic smooth muscle cells (HASMCs). Compared with the control group, Ang II increased cell proliferation by activating MAPKs, including ERK1/2/p90RSK/Akt/mTOR and JNK pathways. However, 6′SL reversed Ang II-stimulated cell proliferation and the ERK1/2/p90RSK/Akt/mTOR pathways in RASMCs and HASMCs. Moreover, 6′SL suppressed Ang II-stimulated cell cycle progression from G0/G1 to S and G2/M phases in RASMCs. Furthermore, 6′SL effectively inhibited cell migration by downregulating NF-κB-mediated MMP2/9 and VCAM-1 expression levels. Interestingly, in RASMCs, 6′SL attenuated Ang II-induced osteogenic switching by reducing the production of p90RSK-mediated c-fos and JNK-mediated c-jun, leading to the downregulation of AP-1-mediated osteopontin production. Taken together, our data suggest that 6′SL inhibits Ang II-induced VSMC proliferation and migration by abolishing the ERK1/2/p90RSK-mediated Akt and NF-κB signaling pathways, respectively, and osteogenic switching by suppressing p90RSK- and JNK-mediated AP-1 activity.
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This research was funded by National Research Foundation of Korea (KNRF-2019R1C1C1007331 and 2022R1A2C4001776).
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Nguyen, T.L.L., Jin, Y., Kim, L. et al. Inhibitory effects of 6′-sialyllactose on angiotensin II-induced proliferation, migration, and osteogenic switching in vascular smooth muscle cells. Arch. Pharm. Res. 45, 658–670 (2022). https://doi.org/10.1007/s12272-022-01404-3
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DOI: https://doi.org/10.1007/s12272-022-01404-3