MiR-27b-3p Correlates with Arteriosclerosis Obliterans and Promotes the Proliferation and Migration of Arterial Smooth Muscle Cells by Targeting GAB1

Patients with atherosclerosis obliterans (ASO) are at risk of amputation or even death if timely treatment is not provided; current clinical treatments for ASO have certain disadvantages. This study aimed to ascertain the function of miR-27b-3p in ASO to provide novel insights for ASO treatment.The...

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Published inInternational Heart Journal Vol. 66; no. 4; pp. 690 - 698
Main Authors Xu, Tuo, Zheng, Changwei, Wu, Yongkang, Chen, Zhengde, Chen, Xiaodong
Format Journal Article
LanguageEnglish
Published Japan International Heart Journal Association 2025
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Abstract Patients with atherosclerosis obliterans (ASO) are at risk of amputation or even death if timely treatment is not provided; current clinical treatments for ASO have certain disadvantages. This study aimed to ascertain the function of miR-27b-3p in ASO to provide novel insights for ASO treatment.The expression of miR-27b-3p in the serum of 117 ASO subjects and 80 healthy individuals was assessed by polymerase chain reaction. Risk factors for coronary artery disease (CAD) in ASO were assessed by multivariate logistic regression analysis. The atherosclerosis cell model was conducted using human vascular smooth muscle cells (HVSMCs) induced with oxidized low-density lipoprotein (ox-LDL). The interaction relationship between miR-27b-3p and GAB1 was assessed using a dual-luciferase reporter assay. HVSMC proliferation and migration were analyzed using the cell counting kit-8 and transwell assay.MiR-27b-3p was upregulated in ASO; it was correlated with ASO severity indicators (ankle-brachial index level and Fontaine stage) and identified as a risk factor for CAD incidence in ASO. Ox-LDL induction in HVSMCs promoted HVSMC proliferation and migration. Overexpression of miR-27b-3p facilitated the proliferation and migration of ox-LDL-induced HVSMCs, which were attenuated by GAB1 overexpression.The upregulation of miR-27b-3p in ASO was correlated with ASO severity and served as a risk factor for CAD in patients with ASO. The potential regulatory mechanism of miR-27b-3p in ASO was the acceleration of vascular smooth muscle cell proliferation and migration by targeting GAB1.
AbstractList Patients with atherosclerosis obliterans (ASO) are at risk of amputation or even death if timely treatment is not provided; current clinical treatments for ASO have certain disadvantages. This study aimed to ascertain the function of miR-27b-3p in ASO to provide novel insights for ASO treatment.The expression of miR-27b-3p in the serum of 117 ASO subjects and 80 healthy individuals was assessed by polymerase chain reaction. Risk factors for coronary artery disease (CAD) in ASO were assessed by multivariate logistic regression analysis. The atherosclerosis cell model was conducted using human vascular smooth muscle cells (HVSMCs) induced with oxidized low-density lipoprotein (ox-LDL). The interaction relationship between miR-27b-3p and GAB1 was assessed using a dual-luciferase reporter assay. HVSMC proliferation and migration were analyzed using the cell counting kit-8 and transwell assay.MiR-27b-3p was upregulated in ASO; it was correlated with ASO severity indicators (ankle-brachial index level and Fontaine stage) and identified as a risk factor for CAD incidence in ASO. Ox-LDL induction in HVSMCs promoted HVSMC proliferation and migration. Overexpression of miR-27b-3p facilitated the proliferation and migration of ox-LDL-induced HVSMCs, which were attenuated by GAB1 overexpression.The upregulation of miR-27b-3p in ASO was correlated with ASO severity and served as a risk factor for CAD in patients with ASO. The potential regulatory mechanism of miR-27b-3p in ASO was the acceleration of vascular smooth muscle cell proliferation and migration by targeting GAB1.
ArticleNumber 24-806
Author Yongkang Wu
Changwei Zheng
Xiaodong Chen
Tuo Xu
Zhengde Chen
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– reference: 34. Chen Z, Wu H, Shi R, et al. miRNAomics analysis reveals the promoting effects of cigarette smoke extract-treated Beas-2B-derived exosomes on macrophage polarization. Biochem Biophys Res Commun 2021; 572: 157-63.
– reference: 13. Zhang M, Chen Y, Niu F, Luo X, Li J, Hu W. MicroRNA-30a-3p: a potential noncoding RNA target for the treatment of arteriosclerosis obliterans. Aging 2023; 15: 11875-90.
– reference: 17. Yang Y, Tang F, Zhao X. miR-27b-3p is highly expressed in serum of patients with preeclampsia and has clinical significance. Endocr Metab Immune Disord Drug Targets 2022; 22: 612-9.
– reference: 15. Li X, Yao N, Zhang J, Liu Z. MicroRNA-125b is involved in atherosclerosis obliterans in vitro by targeting podocalyxin. Mol Med Rep 2015; 12: 561-8.
– reference: 30. Che W, Lerner-Marmarosh N, Huang Q, et al. Insulin-like growth factor-1 enhances inflammatory responses in endothelial cells: role of Gab1 and MEKK3 in TNF-alpha-induced c-Jun and NF-kappaB activation and adhesion molecule expression. Circ Res 2002; 90: 1222-30.
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– reference: 33. Chen D, Si W, Shen J, et al. miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells. Cell Death Dis 2018; 9: 188.
– reference: 16. Cheng F, Yang F, Wang Y, Zhou J, Qian H, Yan Y. Mesenchymal stem cell-derived exosomal miR-27b-3p alleviates liver fibrosis via downregulating YAP/LOXL2 pathway. J Nanobiotechnology 2023; 21: 195.
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– reference: 23. Marchand G. Epidemiology of and risk factors for lower limb arteriopathy obliterans. Ann Cardiol Angeiol (Paris) 2001; 50: 119-27.
– reference: 11. Hess CN, Norgren L, Ansel GM, et al. A structured review of antithrombotic therapy in peripheral artery disease with a focus on revascularization: a TASC (InterSociety consensus for the management of peripheral artery disease) initiative. Circulation 2017; 135: 2534-55.
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– reference: 31. Qian X, Wang H, Wang Y, Chen J, Guo X, Deng H. Enhanced autophagy in GAB1-deficient vascular endothelial cells is responsible for atherosclerosis progression. Front Physiol 2021; 11: 559396.
– reference: 24. Wang X, Lu Y, Zhu L, Zhang H, Feng L. Inhibition of miR-27b regulates lipid metabolism in skeletal muscle of obese rats during hypoxic exercise by increasing PPARγ expression. Front Physiol 2020; 11: 1090.
– reference: 28. Białobrzeska-Paluszkiewicz J, Szostak WB. Risk factors for ischemic heart disease and glycosaminoglycans (GAG's) in plasma in atherosclerosis obliterans. Pol Arch Med Wewn 2003; 110: 951-7.
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– reference: 6. Conte MS, Bradbury AW, Kolh P, et al. Global vascular guidelines on the management of chronic limb-threatening ischemia. J Vasc Surg 2019; 58: S1-S109.
– reference: 25. Prabu P, Rome S, Sathishkumar C, et al. MicroRNAs from urinary extracellular vesicles are non-invasive early biomarkers of diabetic nephropathy in type 2 diabetes patients with the "Asian Indian phenotype" . Diabetes Metab 2019; 45: 276-85.
– reference: 4. Nativel M, Potier L, Alexandre L, et al. Lower extremity arterial disease in patients with diabetes: a contemporary narrative review. Cardiovasc Diabetol 2018; 17: 1-14.
– reference: 7. Morley RL, Sharma A, Horsch AD, Hinchliffe RJ. Peripheral artery disease. Br Med J (Clin Res Ed) 2018; 360: j5842.
– reference: 14. Wang H, Wei Z, Li H, et al. MiR-377-3p inhibits atherosclerosis-associated vascular smooth muscle cell proliferation and migration via targeting neuropilin2. Biosci Rep 2020; 40: BSR20193425.
– reference: 20. Li T, Cao H, Zhuang J, et al. Identification of miR-130a, miR-27b and miR-210 as serum biomarkers for atherosclerosis obliterans. Clin Chim Acta 2011; 412: 66-70.
– reference: 32. Lim S, Park S. Role of vascular smooth muscle cell in the inflammation of atherosclerosis. BMB Rep 2014; 47: 1-7.
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Snippet Patients with atherosclerosis obliterans (ASO) are at risk of amputation or even death if timely treatment is not provided; current clinical treatments for ASO...
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SubjectTerms Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - metabolism
Aged
Arteriosclerosis Obliterans - blood
Arteriosclerosis Obliterans - genetics
Arteriosclerosis Obliterans - metabolism
Case-Control Studies
Cell function
Cell Movement - genetics
Cell Proliferation - genetics
Cells, Cultured
Clinical significance
Expression level
Female
Humans
Lipoproteins, LDL
Male
MicroRNAs - blood
MicroRNAs - genetics
MicroRNAs - metabolism
Middle Aged
Muscle, Smooth, Vascular - cytology
Muscle, Smooth, Vascular - metabolism
Muscle, Smooth, Vascular - pathology
Myocytes, Smooth Muscle - metabolism
Up-Regulation
Vascular smooth muscle cells
Title MiR-27b-3p Correlates with Arteriosclerosis Obliterans and Promotes the Proliferation and Migration of Arterial Smooth Muscle Cells by Targeting GAB1
URI https://www.jstage.jst.go.jp/article/ihj/66/4/66_24-806/_article/-char/en
https://www.ncbi.nlm.nih.gov/pubmed/40738709
Volume 66
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ispartofPNX International Heart Journal, 2025/07/31, Vol.66(4), pp.690-698
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linkProvider Geneva Foundation for Medical Education and Research
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