Effects of miR-125a-3p on Atherosclerotic Plaque, M1/M2 Macrophages, MMP-9 and VEGF

Yanlong LIU; Xuefeng GUANG; Xiaolong YIN; Hailong DAI

doi:10.12259/j.issn.2095-610X.S20220915

Volume 43 Issue 9

Sep. 2022

Turn off MathJax

Article Contents

Article Navigation > Journal of Kunming Medical University > 2022 > 43(9): 1-6

Yanlong LIU, Xuefeng GUANG, Xiaolong YIN, Hailong DAI. Effects of miR-125a-3p on Atherosclerotic Plaque, M1/M2 Macrophages, MMP-9 and VEGF[J]. Journal of Kunming Medical University, 2022, 43(9): 1-6. doi: 10.12259/j.issn.2095-610X.S20220915

Citation:

Yanlong LIU, Xuefeng GUANG, Xiaolong YIN, Hailong DAI. Effects of miR-125a-3p on Atherosclerotic Plaque, M1/M2 Macrophages, MMP-9 and VEGF[J]. Journal of Kunming Medical University, 2022, 43(9): 1-6. doi: 10.12259/j.issn.2095-610X.S20220915

Citation:

PDF( 1766 KB)

Effects of miR-125a-3p on Atherosclerotic Plaque, M1/M2 Macrophages, MMP-9 and VEGF

doi: 10.12259/j.issn.2095-610X.S20220915

Clinical Medicine Center and Key Laboratory for Cardiovascular Disease of Yunnan Province，Dept. of Cardiology，Yan’an Affiliated Hospital of Kunming Medical University，Kunming Yunnan 650051，China

Received Date: 2022-06-26
Available Online: 2022-09-08
Publish Date: 2022-09-29

Abstract

Abstract

Objective To investigate the effects of miR-125a-3p inhibitors on the atherosclerotic plaque formation, M1/M2 macrophages, MMP-9 and VEGF. Methods Fifteen healthy adult male Japanese big-eared rabbits were randomly divided into 3 groups with 5 rabbits in each group. Those in the control group were fed with the normal diet,, those in the atherosclerosis model group were injected with bovine serum albumin and fed with the high cholesterol diet, and those in the miR-125a-3p inhibitor intervention group were injected with miR-125a-3p to interfere with lentivirus vector. The plaque area was determined by image analysis after oil red O staining, MMP-9 and VEGF were determined by immunohistochemistry, and M1 marker CD11c and M2 marker CD206 in plaque tissues were detected by immunofluorescence. Results Compared with the atherosclerosis group, the percentage of plaque area in miR-125a-3p inhibitor group decreased significantly （P < 0.0001）. Compared with the control group, the levels of MMP-9 （P < 0.001）, VEGF （P < 0.01） and CD11c （P < 0.001） increased significantly, and the level of cd206 decreased significantly in the atherosclerosis group （P < 0.001）; Compared with the atherosclerosis group, the levels of MMP-9 （P < 0.01）, VEGF （P < 0.01） and CD11c （P < 0.001） decreased, and the level of cd206 increased in miR-125a-3p inhibitor intervention group （P < 0.001）. Conclusion Inhibition of miR-125a-3p can reduce the formation of atherosclerotic plaques, balance M1/M2 macrophages, and reduce the expression of MMP-9 and VEGF in plaque tissues.miR-125a-3p may be a new target for the treatment of unstable plaques.
- miR-125a-3p inhibitors,
- Atherosclerosis,
- M1/M2 macrophages,
- MMP-9,
- VEGF

FullText(HTML)

References(22)

References

[1]	Moore K J,Sheedy F J,Fisher E A. Macrophages in atherosclerosis:A dynamic balance[J]. Nat Rev Immunol,2013,13(10):709-721. doi: 10.1038/nri3520
[2]	Mills C D,Ley K. M1 and M2 macrophages:The chicken and the egg of immunity[J]. J Innate Immun,2014,6(6):716-726. doi: 10.1159/000364945
[3]	Murray P J,Allen J E,Biswas S K,et al. Macrophage activation and polarization:Nomenclature and experimental guidelines[J]. Immunity,2014,41(1):14-20. doi: 10.1016/j.immuni.2014.06.008
[4]	Schmitz G,Grandl M. Role of redox regulation and lipid rafts in macrophages during Ox-LDL-mediated foam cell formation[J]. Antioxid Redox Signal,2007,9(9):1499-1518. doi: 10.1089/ars.2007.1663
[5]	杨新春,张大鹏. 慢性冠状动脉综合征的概念和要点及意义[J]. 中国心血管病研究,2019,17(10):871-873. doi: 10.3969/j.issn.1672-5301.2019.10.002
[6]	Stoger J L,Gijbels M J,Van Der Velden S,et al. Distribution of macrophage polarization markers in human atherosclerosis[J]. Atherosclerosis,2012,225(2):461-468. doi: 10.1016/j.atherosclerosis.2012.09.013
[7]	Kuznetsova T,Prange K H M,Glass C K,et al. Transcriptional and epigenetic regulation of macrophages in atherosclerosis[J]. Nature Reviews Cardiology,2020,17(4):216-228. doi: 10.1038/s41569-019-0265-3
[8]	Van der Veken B,De Meyer G R,Martinet W. Intraplaque neovascularization as a novel therapeutic target in advanced atherosclerosis[J]. Expert Opin Ther Targets,2016,20(10):1247-1257. doi: 10.1080/14728222.2016.1186650
[9]	徐声波,吴平路,余晖,等. AIS患者CTRP1、MMP-9水平与颈动脉硬化斑块稳定性及神经功能缺损程度的关系[J]. 脑与神经疾病杂志,2021,29(8):492-496.
[10]	Ganta V C,Choi M,Farber C R,et al. Antiangiogenic VEGF165b regulates macrophage polarization via S100A8/S100A9 in peripheral artery disease[J]. Circulation,2019,139(2):226-242. doi: 10.1161/CIRCULATIONAHA.118.034165
[11]	Clemente C,Rius C,Alonso-Herranz L,et al. MT4-MMP deficiency increases patrolling monocyte recruitment to early lesions and accelerates atherosclerosis[J]. Nat Commun,2018,9(1):910. doi: 10.1038/s41467-018-03351-4
[12]	戴海龙,肖娟,潘云. 冠心病患者外周血单核细胞中miR-125a-3p的表达研究[J]. 中国心血管病研究,2020,18(3):203-205. doi: 10.3969/j.issn.1672-5301.2020.03.003
[13]	Mushenkova N V,Nikiforov N G,Melnichenko A A,et al. Functional phenotypes of intraplaque macrophages and their distinct roles in atherosclerosis development and atheroinflammation[J]. Biomedicines,2022,10(2):452. doi: 10.3390/biomedicines10020452
[14]	Barquera S,Pedroza-Tobias A,Medina C,et al. Global overview of the epidemiology of atherosclerotic cardiovascular disease[J]. Arch Med Res,2015,46(5):328-338. doi: 10.1016/j.arcmed.2015.06.006
[15]	Guilliams M,Mildner A,Yona S. Developmental and functional heterogeneity of monocytes[J]. Immunity,2018,49(4):595-613. doi: 10.1016/j.immuni.2018.10.005
[16]	Bouhlel M A,Derudas B,Rigamonti E,et al. PPARgamma activation primes human monocytes into alternative M2 macrophages with anti-inflammatory properties[J]. Cell Metab,2007,6(2):137-143. doi: 10.1016/j.cmet.2007.06.010
[17]	Rupaimoole R,Slack F J. MicroRNA therapeutics:towards a new era for the management of cancer and other diseases[J]. Nat Rev Drug Discov,2017,16(3):203-222. doi: 10.1038/nrd.2016.246
[18]	Bartel D P. MicroRNAs:Genomics,biogenesis,mechanism,and function[J]. Cell,2004,116(2):281-297. doi: 10.1016/S0092-8674(04)00045-5
[19]	Lujambio A,Lowe S W. The microcosmos of cancer[J]. Nature,2012,482(7385):347-355. doi: 10.1038/nature10888
[20]	Lv L L,Feng Y,Wu M,et al. Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury[J]. Cell Death Differ,2020,27(1):210-226. doi: 10.1038/s41418-019-0349-y
[21]	Mao Y,Liu X,Song Y,et al. VEGF-A/VEGFR-2 and FGF-2/FGFR-1 but not PDGF-BB/PDGFR-β play important roles in promoting immature and inflammatory intraplaque angiogenesis[J]. PloS One,2018,13(8):e0201395. doi: 10.1371/journal.pone.0201395
[22]	Bot P T,Pasterkamp G,Goumans M J,et al. Hyaluronic acid metabolism is increased in unstable plaques[J]. Eur J Clin Invest,2010,40(9):818-827. doi: 10.1111/j.1365-2362.2010.02326.x

Relative Articles(20)

Relative Articles

[1]	Daiju TAO, Peng CHEN, Yuqing LI, Linyi CHEN, Renhua YANG, Bo HE, Zhiqiang SHEN. Protective Effect of Corilagin on OX-LDL-Induced HUVECs Cell Damage and Its Impact on the Expression of the MyD88 Signaling Pathway. Journal of Kunming Medical University, 2023, 44(10): 18-25. doi: 10.12259/j.issn.2095-610X.S20231019
[2]	Nihong LU, Honglu LIU, Jiawei XIA, Yangjun CHEN, Linjun SHEN, Yongrui YANG, Jie LI. Clinical Evaluation of Immune Function and SAA, MMP-9 and MMP-14 in Liver Injury Caused by Anti-Tuberculous Drugs. Journal of Kunming Medical University, 2022, 43(4): 50-54. doi: 10.12259/j.issn.2095-610X.S20220410
[3]	Li ZHANG, Yuting WANG, Jianing SHI, Dan YU, Renhua YANG, Zhiqiang SHEN, Jiang LONG, Peng CHEN. Network Pharmacology-based Analysis of the Anti-atherosclerosis Mechanism of Scutellarin and Experimental Validation in Vivo. Journal of Kunming Medical University, 2022, 43(8): 17-27. doi: 10.12259/j.issn.2095-610X.S20220804
[4]	Yang Ke , Dan Zu Jian , Zhou Qiong Hua , Wang Jun Feng . Relationship between Soluble Cytokine Receptors, Matrix Metalloproteinases and Pancreatic Cancer. Journal of Kunming Medical University, 2017, 38(01): 99-102.
[5]	Li Fan, Tong Zong Wu , Yang Chong Meng , Li Juan Juan , Yuan Yun , Wu Chun Yun . . Journal of Kunming Medical University, 2017, 38(05): 16-20.
[6]	Gou Wei Jie . . Journal of Kunming Medical University,
[7]	He Mi . . Journal of Kunming Medical University,
[8]	Lan Dan Feng . . Journal of Kunming Medical University,
[9]	Guan Bing . . Journal of Kunming Medical University,
[10]	Cao Rui . . Journal of Kunming Medical University,
[11]	Li Fan. . Journal of Kunming Medical University,
[12]	Lin Yan . . Journal of Kunming Medical University,
[13]	Chen Li Ling . . Journal of Kunming Medical University,
[14]	Du Ming . . Journal of Kunming Medical University, 2013, 34(12): 1-1.
[15]	Hu Yan Jie . . Journal of Kunming Medical University,
[16]	Wang Ling . The Correlation between Lower Extremity Atherosclerosis and Bone Mineral Density in Type 2 Diabetes Mellitus Patients. Journal of Kunming Medical University,
[17]	. Therapeutic Effect of PAS Combination Therapy on 40 Patients with Atherosclerosis. Journal of Kunming Medical University,
[18]	. Evaluation of Atherosclerosis in Rheumatoid Arthritis Patients with High Lipid Levels by Ultrasonography. Journal of Kunming Medical University,
[19]	Deng Zi Yu . . Journal of Kunming Medical University,
[20]	Qiu Hong Mei . . Journal of Kunming Medical University,