c-Myc Antisense Oligonucleotides Preserve Smooth Muscle Differentiation and Reduce Negative Remodelling following Rat Carotid Arteriotomy

Forte, Amalia; Galderisi, Umberto; Feo, Marisa De; Gomez, Maria F.; Esposito, Salvatore; Santé, P; Renzulli, Attilio; Agozzino, L; Hellstrand, Per; Berrino, Liberato; Cipollaro, Marilena; Cotrufo, Maurizio; Rossi, Francesco; Cascino, A.

doi:10.1159/000085379

Cited by 20 publications

(20 citation statements)

References 57 publications

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“…The contractile phenotype of VSMCs proliferates at an extremely low rate, while the synthetic phenotype, characterized by decreased expression of the above markers, is prone to proliferation [27]. It was reported that c-myc ASO can prevent smooth muscle differentiation in rat carotid injury model [28]. In this rat vein graft model, after reperfusion, VSMCs of the vein grafts would also gradually change from contractile to synthetic phenotype.…”

Section: Discussionmentioning

confidence: 85%

Small Interfering RNA to c-myc Inhibits Vein Graft Restenosis in a Rat Vein Graft Model

Wang

Liu

Shen

et al. 2011

Journal of Surgical Research

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Section: Discussionmentioning

confidence: 85%

Small Interfering RNA to c-myc Inhibits Vein Graft Restenosis in a Rat Vein Graft Model

Wang

Liu

Shen

et al. 2011

Journal of Surgical Research

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“…Total RNA was prepared from the astrocytes using a Micro-to-Midi Total RNA Purification System (Invitrogen). For reverse transcriptase (RT)-PCR analysis, SuperScript One-Step RT-PCR kit with Platinum Taq (Invitrogen) was used with a total volume of 50 l. Specific primer pairs for c-Myc were used as follows (Forte et al, 2005): forward, 5Ј-CTTCCCCTACCCGCT-CAACGAC-3Ј; reverse, 5Ј-CACATCAATTTCTTCCTCATCA-3Ј. As a control, ␤-actin was amplified with the following primers: forward, 5Ј-ACCCACACTGTGCCCATCTAA-3Ј; reverse, 5Ј-GCCACAGGATTCC-ATTACCCAA-3Ј.…”

Section: Methodsmentioning

confidence: 99%

Mild Hypoxia Promotes Survival and Proliferation of SOD2-Deficient Astrocytes via c-Myc Activation

et al. 2006

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Mouse astrocytes deficient in the mitochondrial form of manganese superoxide dismutase (SOD2) do not survive in culture under atmospheric air with 20% oxygen (O 2 ), which is a common condition for cell cultures. Seeding the cells and maintaining them under mild hypoxic conditions (5% O 2 ) circumvents this problem and allows the cells to grow and become confluent. Previous studies from our laboratory showed that this adaptation of the cells was not attributable to compensation by other enzymes of the antioxidant defense system. We hypothesized that transcriptional activity and upregulation of genes other than those with an antioxidant function are involved. Our present study shows that c-Myc was significantly induced and that it inhibited p21 and induced proteins such as cyclindependent kinases, cyclin D, and cyclin E, which are involved in the cell cycle process, along with phosphorylation of the retinoblastoma protein and Cdc2 (cell division cycle 2). These mechanisms contribute to cell proliferation. Small interfering RNA of c-Myc, however, blocked proliferation of SOD2 homozygous (SOD2Ϫ/Ϫ) astrocytes under mild hypoxia consisting of 5% O 2 , whereas it did not affect the growth of wild-type astrocytes. Our results indicate that c-Myc plays a critical role in hypoxia-induced proliferation and survival of SOD2Ϫ/Ϫ astrocytes by overcoming injury caused by oxidative stress.

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“…28 Local Oligo Delivery miRNA inhibitors were delivered into injured vascular tissue using an established protocol. 29 …”

Section: Rat Carotid Artery Balloon Injury Modelmentioning

confidence: 99%

MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation

Cheng

Yue³

et al. 2007

Circulation Research

856

852

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Abstract-MicroRNAs (miRNAs) are a recently discovered class of endogenous, small, noncoding RNAs that regulate about 30% of the encoding genes of the human genome. However, the role of miRNAs in vascular disease is currently completely unknown. Using microarray analysis, we demonstrated for the first time that miRNAs are aberrantly expressed in the vascular walls after balloon injury. The aberrantly expressed miRNAs were further confirmed by Northern blot and quantitative real-time polymerase chain reaction. Modulating an aberrantly overexpressed miRNA, miR-21, via antisense-mediated depletion (knock-down) had a significant negative effect on neointimal lesion formation. In vitro, the expression level of miR-21 in dedifferentiated vascular smooth muscle cells was significantly higher than that in fresh isolated differentiated cells. Depletion of miR-21 resulted in decreased cell proliferation and increased cell apoptosis in a dose-dependent manner. MiR-21-mediated cellular effects were further confirmed in vivo in balloon-injured rat carotid arteries. Western blot analysis demonstrated that PTEN and Bcl-2 were involved in miR-21-mediated cellular effects. The results suggest that miRNAs are novel regulatory RNAs for neointimal lesion formation. MiRNAs may be a new therapeutic target for proliferative vascular diseases such as atherosclerosis, postangioplasty restenosis, transplantation arteriopathy, and stroke. (Circ Res. 2007;100:1579-1588.)Key Words: microRNAs Ⅲ vascular smooth muscle cells Ⅲ proliferation Ⅲ apoptosis Ⅲ neointimal formation M icroRNAs (miRNAs) are endogenous, noncoding, single-stranded RNAs of Ϸ22 nucleotides and constitute a novel class of gene regulators. [1][2][3] Although the first miRNA, lin-4, was discovered in 1993, 4,5 their presence in vertebrates was confirmed only in 2001. 6 MiRNAs are initially transcribed by RNA polymerase II (Pol II) in the nucleus to form large pri-miRNA transcripts. 7 The primiRNAs are processed by the RNase III enzymes, Drosha and Dicer, to generate 18-to 24-nucleotide mature miRNAs. The mature miRNAs negatively regulate gene expression in 1 of 2 ways that depend on the degree of complementarity between the miRNA and its target. MiRNAs that bind to 3ЈUTR of mRNA with imperfect complementarity block protein translation. In contrast, miRNAs that bind to mRNA with perfect complementarity induce targeted mRNA cleavage. Currently, more than 400 miRNAs have been cloned and sequenced in human, and the estimated number of miRNA genes is as high as 1000 in the human genome. 8,9 As a group, miRNAs are estimated to regulate 30% genes of the human genome. 10 Analogous to the first RNA revolution in the 1980s with Cech discovering the enzymatic activity of RNA, 11 this recent discovery of RNAi and miRNA may represent the second RNA revolution. 12 Small interfering RNAs (siRNAs) are another class of small noncoding RNAs that have similar mechanism for gene expression regulation. However, they are different from each other. 5,13 The chief difference lies in their origins....

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c-Myc Antisense Oligonucleotides Preserve Smooth Muscle Differentiation and Reduce Negative Remodelling following Rat Carotid Arteriotomy

Cited by 20 publications

References 57 publications

Small Interfering RNA to c-myc Inhibits Vein Graft Restenosis in a Rat Vein Graft Model

Small Interfering RNA to c-myc Inhibits Vein Graft Restenosis in a Rat Vein Graft Model

Mild Hypoxia Promotes Survival and Proliferation of SOD2-Deficient Astrocytes via c-Myc Activation

MicroRNA Expression Signature and Antisense-Mediated Depletion Reveal an Essential Role of MicroRNA in Vascular Neointimal Lesion Formation

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