Metformin Inhibits high Glucose-induced Vascular Smooth Muscle Cells Proliferation by Promoting Autophagy via AMPK/PPAR-γ

Ziwei ZHANG; Jialin ZHENG; Xiaoyu XU; Hong WANG

doi:10.12259/j.issn.2095-610X.S20231026

Volume 44 Issue 10

Oct. 2023

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Article Navigation > Journal of Kunming Medical University > 2023 > 44(10): 60-66

Ziwei ZHANG, Jialin ZHENG, Xiaoyu XU, Hong WANG. Metformin Inhibits high Glucose-induced Vascular Smooth Muscle Cells Proliferation by Promoting Autophagy via AMPK/PPAR-γ[J]. Journal of Kunming Medical University, 2023, 44(10): 60-66. doi: 10.12259/j.issn.2095-610X.S20231026

Citation:

Ziwei ZHANG, Jialin ZHENG, Xiaoyu XU, Hong WANG. Metformin Inhibits high Glucose-induced Vascular Smooth Muscle Cells Proliferation by Promoting Autophagy via AMPK/PPAR-γ[J]. Journal of Kunming Medical University, 2023, 44(10): 60-66. doi: 10.12259/j.issn.2095-610X.S20231026

Citation:

Ziwei ZHANG, Jialin ZHENG, Xiaoyu XU, Hong WANG. Metformin Inhibits high Glucose-induced Vascular Smooth Muscle Cells Proliferation by Promoting Autophagy via AMPK/PPAR-γ[J]. Journal of Kunming Medical University, 2023, 44(10): 60-66. doi: 10.12259/j.issn.2095-610X.S20231026

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Metformin Inhibits high Glucose-induced Vascular Smooth Muscle Cells Proliferation by Promoting Autophagy via AMPK/PPAR-γ

doi: 10.12259/j.issn.2095-610X.S20231026

Ziwei ZHANG¹,
Jialin ZHENG¹,
Xiaoyu XU^{1, 2},
Hong WANG^{1
,
,}

1.
Center of Coronary Heart Disease，Fuwai Yunnan Cardiovascular Hospital， Kunming Yunnan 650032，China
2.
Graduate School of Kunming Medical University， Kunming Yunnan 650500，China

Received Date: 2023-08-23
Available Online: 2023-09-12
Publish Date: 2023-10-25

Abstract

Abstract

Objective To investigate the effect and regulatory mechanism of metformin on autophagy and cell proliferation of vascular smooth muscle cells （VSMCs） cultured in high glucose in mice aortic. Methods Western blot was used to detect the changes in microtubule-associated protein light chain 3-II （LC3-II） and Beclin-1 protein levels in different treatment groups. Transmission electron microscope was used to observe the the level of autophagosomes in VSMCs of each treatment group. Western blot was used to detect the expression levels of p-AMPK/AMPK and PPAR-γ proteins in different treatment groups. The EDU method was used to detect the proliferation of VSMCs in different treatment groups. Results Metformin and rapamycin reversed the inhibitory effect of high glucose on VSMC autophagy （P < 0.001）. Compound C and GW9662 enhanced the inhibitory effect of high glucose on VSMC autophagy （P < 0.05）. Metformin reversed the negative regulation of high glucose on the AMPK/PPAR-γ pathway （P < 0.01）. Metformin and rapamycin inhibited high glucose-induced VSMC proliferation （P < 0.001）, and Compound C and GW9662 reversed the inhibitory effect of metformin on high glucose-induced VSMC proliferation （P < 0.05）. Conclusion High glucose promotes the proliferation of VSMCs, which may be regulated by autophagy. Metformin can upregulate autophagy levels in VSMCs by activating the AMPK/PPAR-γ pathway, thereby inhibiting the abnormal proliferation of VSMCs induced by high sugar.
- Metformin,
- High glucose,
- Autophagy,
- Vascular smooth muscle cell,
- Proliferation

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References(24)

References

[1]	Chiong M,Morales P,Torres G,et al. Influence of glucose metabolism on vascular smooth muscle cell proliferation[J]. Vasa,2013,42(1):8-16. doi: 10.1024/0301-1526/a000243
[2]	Yang M,Fang J,Liu Q,et al. Role of ROS-TRPM7-ERK1/2 axis in high concentration glucose-mediated proliferation and phenotype switching of rat aortic vascular smooth muscle cells[J]. Biochemical and Biophysical Research Communications,2017,494(3-4):526-533. doi: 10.1016/j.bbrc.2017.10.122
[3]	Marino G,Niso-Santano M,Baehrecke E H,et al. Self-consumption: The interplay of autophagy and apoptosis[J]. Nat Rev Mol Cell Biol,2014,15(2):81-94. doi: 10.1038/nrm3735
[4]	Wu H,Song A,Hu W,et al. The anti-atherosclerotic effect of paeonol against vascular smooth muscle cell proliferation by up-regulation of autophagy via the AMPK/mTOR signaling pathway[J]. Frontiers in Pharmacology,2018,8:948. doi: 10.3389/fphar.2017.00948
[5]	张紫微,杨丽霞,吕晋琳,等. 血管紧张素Ⅱ诱发自噬对血管平滑肌细胞表型转换的调控作用[J]. 中国动脉硬化杂志,2017,25(5):452-456.
[6]	Phadwal K,Feng D,Zhu D,et al. Autophagy as a novel therapeutic target in vascular calcification[J]. Pharmacology & Therapeutics,2020,206:107430.
[7]	Peng S,Xu L,Che X,et al. Atorvastatin inhibits inflammatory response,attenuates lipid deposition,and improves the stability of vulnerable atherosclerotic plaques by modulating autophagy[J]. Frontiers in Ppharmacology,2018,9:438. doi: 10.3389/fphar.2018.00438
[8]	Poznyak A V,Litvinova L,Poggio P,et al. From diabetes to atherosclerosis: Potential of metformin for management of cardiovascular disease[J]. International Journal of Molecular Sciences,2022,23(17):9738. doi: 10.3390/ijms23179738
[9]	Yang Q,Yuan H,Chen M,et al. Metformin ameliorates the progression of atherosclerosis via suppressing macrophage infiltration and inflammatory responses in rabbits[J]. Life Sciences,2018,198:56-64. doi: 10.1016/j.lfs.2018.02.017
[10]	Wu H,Feng K,Zhang C,et al. Metformin attenuates atherosclerosis and plaque vulnerability by upregulating KLF2-mediated autophagy in apoE−/-mice[J]. Biochemical and Biophysical Research Communications,2021,557:334-341. doi: 10.1016/j.bbrc.2021.04.029
[11]	Phadwal K,Koo E,Jones R A,et al. Metformin protects against vascular calcification through the selective degradation of Runx2 by the p62 autophagy receptor[J]. Journal of Cellular Physiology,2022,237(11):4303-4316. doi: 10.1002/jcp.30887
[12]	Yang B,Gao X,Sun Y,et al. Dihydroartemisinin alleviates high glucose-induced vascular smooth muscle cells proliferation and inflammation by depressing the miR-376b-3p/KLF15 pathway[J]. Biochemical and Biophysical Research Communications,2020,530(3):574-580. doi: 10.1016/j.bbrc.2020.07.095
[13]	Yuan T,Yang T,Chen H,et al. New insights into oxidative stress and inflammation during diabetes mellitus-accelerated atherosclerosis[J]. Redox Biology,2019,20:247-260. doi: 10.1016/j.redox.2018.09.025
[14]	Tiong Y L,Ng K Y,Koh R Y,et al. Melatonin inhibits high glucose-induced ox-LDL/LDL expression and apoptosis in human umbilical endothelial cells[J]. Hormone Molecular Biology and Clinical Investigation,2020,41(4):20200009. doi: 10.1515/hmbci-2020-0009
[15]	Zhao Y,Lu N,Zhang Y,et al. High glucose induced rat aorta vascular smooth muscle cell oxidative injury: Involvement of protein tyrosine nitration[J]. Journal of Physiology and Biochemistry,2011,67(4):539-549. doi: 10.1007/s13105-011-0099-x
[16]	Liu J,Wu J,Sun A,et al. Hydrogen sulfide decreases high glucose/palmitate-induced autophagy in endothelial cells by the Nrf2-ROS-AMPK signaling pathway[J]. Cell & Bioscience,2016,6(1):1-17.
[17]	Xu K,Liu X,Ke Z,et al. Resveratrol modulates apoptosis and autophagy induced by high glucose and palmitate in cardiac cells[J]. Cellular Physiology and Biochemistry,2018,46(5):2031-2040. doi: 10.1159/000489442
[18]	De Jager J,Kooy A,Schalkwijk C,et al. Long‐term effects of metformin on endothelial function in type 2 diabetes: A randomized controlled trial[J]. Journal of Internal Medicine,2014,275(1):59-70. doi: 10.1111/joim.12128
[19]	Van der Aa M P,Elst M,Van De Garde E,et al. Long-term treatment with metformin in obese,insulin-resistant adolescents: Results of a randomized double-blinded placebo-controlled trial[J]. Nutrition & Diabetes,2016,6(8):e228.
[20]	He X,Chen X,Wang L,et al. Metformin ameliorates Ox-LDL-induced foam cell formation in raw264.7 cells by promoting ABCG-1 mediated cholesterol efflux[J]. Life Sciences,2019,216:67-74. doi: 10.1016/j.lfs.2018.09.024
[21]	Gopoju R,Panangipalli S,Kotamraju S. Metformin treatment prevents SREBP2-mediated cholesterol uptake and improves lipid homeostasis during oxidative stress-induced atherosclerosis[J]. Free Radical Biology and Medicine,2018,118:85-97. doi: 10.1016/j.freeradbiomed.2018.02.031
[22]	You G,Long X,Song F,et al. Metformin activates the AMPK-mTOR pathway by modulating lncRNA TUG1 to induce autophagy and inhibit atherosclerosis[J]. Drug Design,Development and Therapy,2020,14:457. doi: 10.2147/DDDT.S233932
[23]	Faghfouri A H,Khajebishak Y,Payahoo L,et al. PPAR-gamma agonists: Potential modulators of autophagy in obesity[J]. European Journal of Pharmacology,2021,912:174562. doi: 10.1016/j.ejphar.2021.174562
[24]	Wang H,Wang A,Wang X,et al. AMPK/PPAR-γ/NF-κB axis participates in ROS-mediated apoptosis and autophagy caused by cadmium in pig liver[J]. Environmental Pollution,2022,294:118659. doi: 10.1016/j.envpol.2021.118659

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