MicroRNA-17-5p, a novel endothelial cell modulator, controls vascular re-endothelialization and neointimal lesion formation

Background The functions of miR-17-5p in tumorigenesis have been explored. However, their functionalities in arterial endothelial cells (ECs) have not been investigated. Besides, the issue of vascular remodelling is barely addressed. Objectives The study aimed to determine the effect of overexpression or inhibition of miR-17-5p on arterial endothelial cells’ (ECs) function and vascular remodelling in vitro and the rat carotid arteries model. Methods Quantitative RT-PCR analysis was performed to examine the expression of miR-17-5p. Then, gain-of-function and loss-of-function approaches were employed to investigate the functional roles of miR-17-5p in cultured human coronary artery endothelial cells (HCAECs); further, TargetScan software analysis and luciferase reporter activity assay were performed to investigate the potential mechanism. Lastly, the results of the cell segment were verified in a rat carotid artery balloon injury model by Western blot analysis, measurement of the vascular cGMP level and plasma 8-iso-prostaglandin F2 (8-iso-PGF2) testing. Moreover, morphometric analysis was implemented to detect the re-endothelialization and neointimal formation in rat carotid artery after balloon injury. Results This study firstly found that miR-17-5p expression was upregulated in the injured vascular walls and highly expressive in ECs; overexpression of miR-17-5p inhibited HCAECs’ proliferation and migration, whereas miR-17-5p knockdown strengthened its proliferative and migratory roles, influenced inflammatory response, through regulating VEGRA and VEGFR2. It was found that miR-17-5p bind to VEGFA and VEGFR2 at the 3′UTR. Next, downregulation of miR-17-5p promotes re-endothelialization, and attenuates neointimal formation as measured by the I/M ratio (0.63±0.05 vs 1.45±0.06, antagomiR-17-5p vs. Lenti-NC, p < 0.05). In addition, the functional recovery of the endothelium was also accelerated by miR-17-5p knockdown. Conclusion Our study suggests that miR-17-5p is a feasible strategy for the selective modulation of endothelialization and vascular remodelling through regulating VEGFA and VEGFR2.

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Carotid Stent Restenosis and Thrombosis in Rabbits: The Effect of Antiplatelet Agents

Journal of Cardiovascular Pharmacology and Therapeutics ◽

10.1177/1074248420931624 ◽

2020 ◽

Vol 25 (6) ◽

pp. 570-577

Author(s):

Nikolaos P. E. Kadoglou ◽

Marianna Stasinopoulou ◽

Triantafyllos Giannakopoulos ◽

Anastasios Papapetrou ◽

Constantinos Dimitriou ◽

...

Keyword(s):

High Fat Diet ◽

Carotid Arteries ◽

Antiplatelet Agents ◽

Balloon Injury ◽

Neointimal Formation ◽

Total Occlusion ◽

Stent Restenosis ◽

Vascular Walls ◽

New Zealand White Rabbits ◽

Group 3

Background: The purpose of the study was the comparative assessment of ticagrelor and clopidogrel effects on carotid post-balloon injury (PBI) and on post carotid artery stenting (CAS) rate of in-stent restenosis (ISR) and in-stent thrombosis in atherosclerotic rabbits. Methods: Forty-eight New Zealand white rabbits on high-fat diet were randomized into 4 groups: A1: PBI and clopidogrel (30 mg/kg/d), A2: PBI and ticagrelor (21 mg/kg twice daily), B1: PBI, CAS, and clopidogrel (30 mg/kg/d), B2: PBI, CAS, and ticagrelor (21 mg/kg twice daily). All rabbits received orally aspirin (10 mg/kg/d) and interventions were performed in their right carotid arteries (RCAs). Optical coherence tomography (OCT) and carotid angiography were performed at end point, while platelet aggregation and lipid profile were measured. After euthanasia both carotids were obtained for histological examination. Results: In B1 group, 3 rabbits presented thrombotic total occlusion of the stents, while none such episode was observed in B2 group. The neointimal areas in RCAs, calculated by OCT, did not differ between A1 and A2 groups, and between B1 and B2 groups ( P > .05). From the histological findings, the intima/(media + intima) percentage (%) in RCAs of balloon-injured rabbits did not present any difference between groups ( P = .812). Similarly, the immunohistochemically determined accumulation of endothelial cells and macrophages on vascular walls was equivalent between groups ( P > .05). Conclusion: Following carotid balloon injury and stenting, clopidogrel and ticagrelor did not show any differential effects on the extent of neointimal formation and ISR in atherosclerotic rabbits receiving aspirin. Three thrombotic stent occlusions were noted in the clopidogrel treatment group, but this finding was not statistically significant.

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Fibrin glue containing fibroblast growth factor type 1 and heparin with autologous endothelial cells reduces intimal hyperplasia in a canine carotid artery balloon injury model

Journal of Vascular Surgery ◽

10.1016/s0741-5214(97)70213-1 ◽

1997 ◽

Vol 25 (5) ◽

pp. 840-849 ◽

Cited By ~ 29

Author(s):

Joseph I. Zarge ◽

Peter Huang ◽

Vicki Husak ◽

Dae Un Kim ◽

Christian C. Haudenschild ◽

...

Keyword(s):

Endothelial Cells ◽

Growth Factor ◽

Carotid Artery ◽

Fibroblast Growth Factor ◽

Intimal Hyperplasia ◽

Fibroblast Growth ◽

Balloon Injury ◽

Injury Model ◽

Factor Type

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Inhibitory effect of low-dose estrogen on neointimal formation after balloon injury of rat carotid artery

European Journal of Pharmacology ◽

10.1016/j.ejphar.2004.09.011 ◽

2004 ◽

Vol 502 (3) ◽

pp. 265-270 ◽

Cited By ~ 5

Author(s):

Tokumitsu Watanabe ◽

Yukiko Miyahara ◽

Masahiro Akishita ◽

Takashi Nakaoka ◽

Naohide Yamashita ◽

...

Keyword(s):

Carotid Artery ◽

Low Dose ◽

Inhibitory Effect ◽

Balloon Injury ◽

Neointimal Formation

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Perivascular gene transfer of dominant-negative N19RhoA attenuates neointimal formation via inhibition of TGF-β1-Smad2 signaling in rats after carotid artery balloon injury

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2009.08.104 ◽

2009 ◽

Vol 389 (2) ◽

pp. 217-223 ◽

Cited By ~ 7

Author(s):

WenDong Chen ◽

YuFeng Chu ◽

DingLiang Zhu ◽

Chen Yan ◽

JianJun Liu ◽

...

Keyword(s):

Gene Transfer ◽

Carotid Artery ◽

Dominant Negative ◽

Balloon Injury ◽

Neointimal Formation ◽

Tgf Β1

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Inhibition of neointimal formation by targeted delivery of porcine coronary arterial endothelial cells overexpressing interleukin-8 (IL8) receptors in pig coronary arteries after stent implantation

Journal of the American Society of Hypertension ◽

10.1016/j.jash.2015.03.285 ◽

2015 ◽

Vol 9 (4) ◽

pp. e123

Author(s):

Samantha S. Giordano ◽

Gregory Walcott ◽

Brigitta Brott ◽

Daisy Xing ◽

Peter Anderson ◽

...

Keyword(s):

Endothelial Cells ◽

Coronary Arteries ◽

Stent Implantation ◽

Targeted Delivery ◽

Interleukin 8 ◽

Neointimal Formation ◽

Pig Coronary Arteries ◽

Arterial Endothelial Cells

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Systemic Depletion of Macrophages by Liposomal Bisphosphonates Reduces Neointimal Formation Following Balloon-Injury in the Rat Carotid Artery

Journal of Cardiovascular Pharmacology ◽

10.1097/00005344-200311000-00014 ◽

2003 ◽

Vol 42 (5) ◽

pp. 671-679 ◽

Cited By ~ 52

Author(s):

Haim D. Danenberg ◽

Ilia Fishbein ◽

Hila Epstein ◽

Johannes Waltenberger ◽

Evgeny Moerman ◽

...

Keyword(s):

Carotid Artery ◽

Balloon Injury ◽

Neointimal Formation

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miR-1226-3p Promotes eNOS Expression of Pulmonary Arterial Endothelial Cells to Mitigate Hypertension in Rats via Targeting Profilin-1

BioMed Research International ◽

10.1155/2021/1724722 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Jie Jian ◽

Liang Xia

Keyword(s):

Endothelial Cells ◽

Systolic Pressure ◽

Luciferase Reporter ◽

Regulation Mechanism ◽

Sprague Dawley ◽

Ventricular Systolic Pressure ◽

Binding Effect ◽

Pulmonary Arterial ◽

The Right ◽

Arterial Endothelial Cells

In pulmonary arterial hypertension (PAH), microRNAs (miRNAs) are related with dysfunction of pulmonary arterial endothelial cells. miR-1226-3p was found to be downregulated in the serum of PAH patients, while few studies have illustrated the regulation mechanism of miR-1226-3p on PAH. In this study, we aimed to systematically investigate the role of miR-1226-3p in PAH. Sprague-Dawley (SD) rats were treated with monocrotaline (MCT) to establish the PAH models. The right ventricular systolic pressure (RVSP), ratio of the right ventricle to the left ventricle with septum (RV/(LV+S) ratio), and nitric oxide (NO) content were used to reflect the symptom of the rats. The rat models were used to observe the regulation mechanism of miR-1226-3p on PAH, and dual-luciferase reporter assay was used to verify the binding effect of miR-1226-3p to Pfn1. Besides, the qRT-PCR and western blot were used to measure the expression levels of miR-1226-3p and some keys proteins such as eNOS and Pfn1, respectively. The results showed that the PAH models were established successfully. The RVSP levels and the RV/(LV+S) ratio of the PAH rats were higher than those indexes in normal rats, while the NO content showed the opposite trends. Besides, the decreased miR-1226-3p and eNOS were, respectively, found in the PAH rats and rPAECs, and overexpressed miR-1226-3p could reverse the disadvantages of the PAH rats including increased RVSP, high RV/(LV+S) ratio, and decreased NO content. Furthermore, miR-1226-3p could directly target the 3 ′ -UTR of Profilin-1 (Pfn1). Overexpressed Pfn1 led to decreased eNOS, while miR-1226-3p could partly inhibit the expression of Pfn1 and increase the expression level of eNOS in rPAECs. In summary, this study suggests miR-1226-3p as a protector to increase eNOS, improve NO content in rPAECs of the PAH rats via targeting Pfn, and finally protect the rats from the injury induced by PAH.

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Hsa_circ_0003204 Knockdown Weakens Ox-LDL-Induced Cell Injury by Regulating miR-188-3p/TRPC6 Axis in Human Carotid Artery Endothelial Cells and THP-1 Cells

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.731890 ◽

2021 ◽

Vol 8 ◽

Author(s):

Wenjia Peng ◽

Shuai Li ◽

Shiyue Chen ◽

Jiacheng Yang ◽

Ze Sun

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Carotid Artery ◽

Inflammatory Response ◽

Transient Receptor Potential ◽

Cell Injury ◽

Density Lipoprotein ◽

Luciferase Reporter ◽

Circular Rnas ◽

Human Carotid

Background: Circular RNAs (circRNAs) are involved in atherosclerosis (AS) development. However, the function and mechanism of circRNA hsa_circ_0003204 (circ_0003204) in carotid artery AS remain unclear.Methods: Oxidized low-density lipoprotein (ox-LDL)-treated human carotid artery endothelial cells (HCtAECs) and THP-1 cells were used as cell models of carotid artery AS. Relative levels of circ_0003204, microRNA-188-3p (miR-188-3p), and transient receptor potential canonical channel 6 (TRPC6) were detected by quantitative reverse transcription–polymerase chain reaction or Western blotting. The targeting relationship between circ_0003204 or TRPC6 and miR-188-3p was assessed via dual-luciferase reporter analysis and RNA immunoprecipitation. Cell proliferation was assessed via 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay and 5-ethynyl-2′-deoxyuridine (EdU) assay. Cell apoptosis was analyzed via assessing cell caspase-3 activity, apoptosis, and apoptosis-related protein. Inflammatory response was analyzed via analysis of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Oxidative stress was assessed via determination of reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD).Results: Circ_0003204 and TRPC6 levels were elevated, and miR-188-3p expression declined in ox-LDL-treated HCtAECs and THP-1 cells. Circ_0003204 could regulate TRPC6 expression via mediating miR-188-3p. Circ_0003204 silencing weakened ox-LDL-induced viability inhibition and apoptosis in HCtAECs, and inflammatory response and oxidative stress in THP-1 cells via regulating miR-188-3p. MiR-188-3p overexpression attenuated ox-LDL-induced injury in HCtAECs and THP-1 cells by targeting TRPC6.Conclusion: Circ_0003204 knockdown mitigated ox-LDL-induced injury in HCtAECs and THP-1 cells via regulating the miR-188-3p/TRPC6 axis, indicating that circ_0003204 might play an important role in carotid artery AS.

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