Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype

Ohnaka, Motoaki; Marui, Akira; Yamahara, Kenichi; Minakata, Kenji; Yamazaki, Kazuhiro; Kumagai, Masaya; Masumoto, Hidetoshi; Tanaka, Shiro; Ikeda, Tadashi; Sakata, Ryuzo

doi:10.1016/j.jtcvs.2013.11.054

Cited by 27 publications

(25 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Ohnaka et al . [18] revealed that upregulation of miR-145 induced the phenotypic transformation of vascular smooth muscle cells in rabbit vein graft models. The study focused on the effects of miRNAs in endothelial dysfunction induced by mechanical stretch.…”

Section: Discussionmentioning

confidence: 99%

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

Dong

Zhang

Wang

et al. 2017

Chinese Medical Journal

View full text Add to dashboard Cite

Background:Vein graft failure (VGF) is a serious complication of coronary artery bypass graft, although the mechanism remains unclear. The study aimed to investigate the effects of microRNAs (miRNAs) on the endothelial dysfunction involved in VGF.Methods:Human umbilical vein endothelial cells (HUVECs) were subjected to mechanical stretch stimulation to induce endothelial dysfunction. Genome-wide transcriptome profiling was performed using the Human miRNA OneArray® V4 (PhalanxBio Inc., San Diego, USA). The miRNA-messenger RNA (mRNA) network was investigated using gene ontology and Kyoto Encyclopedia of Genes and Genomes. The miR-551b-5p mimic and inhibitor were applied to regulate miR-551b-5p expression in the HUVECs. The 5-ethynyl-2’-deoxyuridine assay, polymerase chain reaction (PCR), and Western blotting (WB) were used to assess HUVECs proliferation, mRNA expression, and protein expression, respectively. The vein graft model was established in early growth response (Egr)-1 knockout (KO) mice and wide-type (WT) C57BL/6J mice for pathological and immunohistochemical analysis. Endothelial cells isolated from the veins of WT and Egr-1 KO mice were subjected to mechanical stretch stimulation; PCR and WB were conducted to confirm the regulatory effect of Egr-1 on Intercellular adhesion molecule (Icam-1). One-way analysis of variance and independent t-test were performed for data analysis.Results:Thirty-eight miRNAs were differentially expressed in HUVECs after mechanical stretch stimulation. The bioinformatics analysis revealed that Egr-1 might be involved in VGF and was a potential target gene of miR-551b-5p. The mechanical stretch stimulation increased miR-551b-5p expression by 2.93 ± 0.08 fold (t = 3.07, P < 0.05), compared with the normal HUVECs. Transfection with the miR-551b-5p mimic or inhibitor increased expression of miR-551b-5p by 793.1 ± 171.6 fold (t = 13.84, P < 0.001) or decreased by 26.3% ± 2.4% (t = 26.39, P < 0.05) in the HUVECs, respectively. HUVECs proliferation and EGR-1 mRNA expression were significantly suppressed by inhibiting miR-551b-5p expression (P < 0.05). The lumens of the vein grafts in the Egr-1 KO mice were wider than that in the WT mice. Icam-1 expression was suppressed significantly in the Egr-1 KO vein grafts (P < 0.05).Conclusions:Increased miR-551b-5p expression leads to endothelial dysfunction by upregulating Egr-1 expression. EGR-1 KO can improve the function of a grafted vein through suppressing Icam-1.

show abstract

Section: Discussionmentioning

confidence: 99%

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

Dong

Zhang

Wang

et al. 2017

Chinese Medical Journal

View full text Add to dashboard Cite

show abstract

“…In fact, increased VSMC proliferation is cause of vein graft stenosis and failure. In line, the transduction of miR-145 into a rabbit vein used for bypass grafting prevented vein graft disease by regulation of VSMC phenotype [47]. On the other side, miR-143/ 145 deficiency was reported to attenuate the progression of plaque formation in a mouse model of atherosclerosis [48], indicating that more research is necessary to clarify the role on this miRNA cluster in vascular disease.…”

Section: Mirna Expressed In Vascular Cellsmentioning

confidence: 99%

Noncoding RNAs in diabetes vascular complications

Beltrami

Angelini

Emanueli

2015

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

“…Circulating levels of some miRs were down-regulated in patients with coronary artery disease [6], and the patients with type 2 diabetes had less circulating endothelial miR-126 [7]. In vitro experiments showed that miR-125b [1, 8], miR-145 [9] and miR-146a [10] played a regulative role in the aberrant VSMC proliferation, which is a key pathological process of proliferative vascular diseases, such as atherosclerosis or vascular calcification.…”

Section: Introductionmentioning

confidence: 99%

miR-135a Suppresses Calcification in Senescent VSMCs by Regulating KLF4/STAT3 Pathway

Lin¹,

He²,

Xi³

et al. 2016

CVP

View full text Add to dashboard Cite

Cellular function phenotype is regulated by various microRNAs (miRs), including miR-135a. However, how miR-135a is involved in the calcification in senescent vascular smooth muscle cells (VSMCs) is not clear yet. In the present study, we first identified the significantly altered miRNAs in VSMCs, then performed consecutive passage culture of VSMCs and analyzed the expression of miR-135a and calcification genes in the senescent phase. Next, the effects of the miR-135a inhibition on calcification and calcification genes were analyzed. The luciferase assay was used to validate the target protein of miR-135a. The western blotting was used to determine the effects of miR-135a on Krüppel-like factor 4 (KLF4) and signal transducer and activator of transcription 3 protein (STAT3) expression, as well as the relationship between KLF4 and STAT3. Finally, the quantified cellular calcification was measured to examine the involvement of miR-135a, KLF4 and STAT3 in VSMCs calcification. Our results showed that miR-135a was significantly altered in VSMCs. Cell calcification and calcification genes were greatly altered by miR-135a inhibition. KLF4 was validated as the target RNA of miR-135a. Expression of KLF4 and STAT3 were both significantly decreased by over expressed miR-135a, while the inhibition of miR-135a and KLF4 siRNA both decreased the STAT3 protein levels. Moreover, the inhibition of miR-135a dramatically increased the calcium concentration, but co-treatment with KLF4 or STAT3 siRNA both decreased the calcium concentration. The present study identified miR-135a as a potential osteogenic differentiation suppressor in senescent VSMCs and revealed that KLF4/STAT3 pathway, at least partially, was involved in the mechanism.

show abstract

Effect of microRNA-145 to prevent vein graft disease in rabbits by regulation of smooth muscle cell phenotype

Abstract: Nonviral transduction of miR-145 into the bypass graft could be a novel option for preventing intimal hyperplasia in vein graft disease.

Cited by 27 publications

References 26 publications

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

MiR-551b-5p Contributes to Pathogenesis of Vein Graft Failure via Upregulating Early Growth Response-1 Expression

Noncoding RNAs in diabetes vascular complications

miR-135a Suppresses Calcification in Senescent VSMCs by Regulating KLF4/STAT3 Pathway

Contact Info

Product

Resources

About