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Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells

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Abstract

The formation of fat-laden foam cells, contributing to the fatty streaks of the plaques of atheroma, is the critical early process in atherosclerosis. The previous study demonstrated that vascular smooth muscle cells (VSMCs) contain a much larger burden of the excess cholesterol in comparison with monocyte-derived macrophages in human coronary atherosclerosis, as the main origin of foam cells. It is noteworthy that VSMC-derived foam cells are deposited in subintima but not media, where VSMCs normally deposit in. Therefore, migration from media to intima is an indispensable step for a VSMC to accrue neutral lipids and form foam cell. Whether this migration occurs paralleled with or prior to the formation of foam cell is still unclear. Herein, the present study was designed to test the VSMC migratory capability in the process of foam cell formation induced by oxidized low-density lipoprotein (oxLDL). In conclusion, we provide evidence that oxLDL induces the VSMC-derived foam cells formation with increased migration ability and MMP-9 expression, which were partly attributed to the impaired SIRT1 and enhanced nuclear factor-kappa B (NF-κB) activity. As activation of transient receptor potential vanilloid type 1 (TRPV1) has been reported to have anti-atherosclerotic effects, we investigated its role in oxLDL-treated VSMC migration. It is found that activating TRPV1 by capsaicin inhibits VSMC foam cell formation and the accompanied migration through rescuing the SIRT1 and suppressing NF-κB signaling. The present study provides evidence that SIRT1 may be a promising intervention target of atherosclerosis, and raises the prospect of TRPV1 in prevention and treatment of atherosclerosis.

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Acknowledgments

This work was supported by National Natural Science Foundation of China (NSFC 81471193 to Li-Li Zhang, 81271282 to Jing-Cheng Li and 81400967 to Yan Pi).

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Authors and Affiliations

  1. Department of Neurology, Institute of Surgery Research, Daping Hospital, Third Military Medical University, 10 Changjiang Branch Road, Yuzhong District, Chongqing, 400042, People’s Republic of China

    Ming-Jie Zhang, Yi Zhou, Lei Chen, Xu Wang, Yan Pi, Chun-Yan Long, Meng-Jiao Sun, Xue Chen, Chang-Yue Gao, Jing-Cheng Li & Li-Li Zhang

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  1. Ming-Jie Zhang
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  2. Yi Zhou
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  3. Lei Chen
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  4. Xu Wang
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  5. Yan Pi
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Correspondence to Jing-Cheng Li or Li-Li Zhang.

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Figure S1

Identification of primary VSMCs from WT mice by immunofluorescence. Primary VSMCs from WT mice were stained with α-SMA (red fluorescence). Cell nuclei were counterstained with DAPI (blue fluorescence). Scale bar = 40μm. (JPEG 187 kb)

Figure S2

Identification of primary VSMCs from WT mice by flow cytometry. Overlay histogram showed primary VSMCs from WT mice stained with α-SMA (orange line). Isotype control antibody (blue line) was rabbit IgG (monoclonal). Unlabeled control (red line) was cells without incubation with primary antibody and secondary antibody. Over 96% of primary cultured cells were α-SMA positive cells, namely VSMCs, under our experimental conditions. (JPEG 835 kb)

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Zhang, MJ., Zhou, Y., Chen, L. et al. Impaired SIRT1 promotes the migration of vascular smooth muscle cell-derived foam cells. Histochem Cell Biol 146, 33–43 (2016). https://doi.org/10.1007/s00418-016-1408-9

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