Tissue-selective expression of dominant-negative proteins for the regulation of vascular smooth muscle cell proliferation

Jf, Schmitt; Mc, Keogh; Dennehy, Ulla; Chen, D; Lupu, Florea; Weston, Kathleen; Taylor, Derek J.; Vv, Kakkar; Nr, Lemoine

doi:10.1038/sj.gt.3300927

Cited by 12 publications

(6 citation statements)

References 42 publications

(53 reference statements)

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“…AS-ODN-c-myb, antigenes, and dominant-negative c-myb constructs have all been shown to increase apoptosis in various cell lines. 14 -16 Recently, Schmitt et al 24 showed a reduction in rat and rabbit VSMC proliferation and induction of apoptosis in vitro after exposure to c-myb dominant-negative constructs, supporting the findings of the present study, in which AS-ODN-c-myb induced apoptosis of porcine VSMCs. In contrast, apoptosis of PAECs was not enhanced, indicating that as previously suggested, cell fate is modulated in a cell type-specific manner.…”

Section: Inhibition Of C-myb and Apoptosis In Vitrosupporting

confidence: 79%

“…However, it is now known that cell-cycle dysregulation may under certain circumstances, and especially when proliferation is the background driving force, result in apoptosis. 23 Induction of apoptosis after c-myb dysregulation has been suggested by Piacentini et al 14 and Schmitt et al,24 who demonstrated that transfection of rat, rabbit, and human VSMCs with dominant-negative c-myb gene constructs caused not only a decrease in proliferation but also induced apoptosis. Therefore, inhibition of c-Myb induces apoptosis, and this may subsequently reduce neointimal hyperplasia; however, this possible mechanism of action of AS-ODN-cmyb has not previously been investigated.…”

mentioning

confidence: 99%

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Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c- myb After Angioplasty of Porcine Coronary Arteries

Lambert

Malik²,

Shepherd³

et al. 2001

ATVB

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Abstract-Previous studies have shown that inhibition of the proto-oncogene c-myb inhibits neointimal formation in various animal models. However, the temporal and spatial expression of c-Myb in the vessel wall after injury is not known, and the mechanism of action of antisense oligonucleotide (AS-ODN-c-myb) inhibition remains unclear. One potential effect of cell cycle dysregulation by inhibition of c-myb is an increase in the rates of apoptosis. In this study, c-Myb expression after percutaneous transluminal coronary angioplasty (PTCA) injury and induction of apoptosis after AS-ODN-c-myb treatment were determined. Immunohistochemistry and cellular phenotyping were used to localize c-Myb expression in porcine coronary arteries at various time intervals after PTCA. In vitro, the effects of AS-ODN-c-myb on the apoptosis of porcine vascular smooth muscle cells (PVSMCs) and endothelial cells were determined by using a cell-death ELISA and time-lapse video microscopy. In vivo, local delivery of AS-ODN-c-myb was performed after PTCA of pig coronary arteries, and apoptosis was quantified at 6 hours. c-Myb is induced in pig coronary arteries after angioplasty, with maximal expression in inflammatory cells at 18 hours and in vascular smooth muscle cells at 3 to 7 days. In vitro, AS-ODN-c-myb enhanced PVSMCs (6.8Ϯ0.8% [PϭϽ0.001] versus 0.5% serum) but not endothelial cell apoptosis (1.4Ϯ0.5% [PϭNS] versus 0.5% serum). In vivo, 6 hours after porcine coronary angioplasty and delivery of AS-ODN-c-myb, the proportion of apoptotic cells within the media was 4.2Ϯ0.8% (PTCA alone), 2.3Ϯ0.2% (PTCAϩvehicle), and 9.0Ϯ1.1% (PTCAϩAS-ODN-c-myb; PϽ0.05 versus PTCA alone and PϽ0.01 versus PTCAϩsaline). c-Myb is expressed after PTCA of pig coronary arteries, and AS-ODN-c-myb induces apoptosis

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Section: Inhibition Of C-myb and Apoptosis In Vitrosupporting

confidence: 79%

mentioning

confidence: 99%

Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c- myb After Angioplasty of Porcine Coronary Arteries

Lambert

Malik²,

Shepherd³

et al. 2001

ATVB

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show abstract

“…4 Similarly, two anti-allergic drugs, tranilast and perimolast, have shown recent promise and may act through suppression of TGF-␤1. 5,6 Positive results have also been reported with blockade of thrombin, 7 angiotensin 11, 8 c-myc and c-myb 9 activity. However, molecularly directed treatments will have to perform well when compared with the latest results using vascular brachytherapy for prevention of restenosis.…”

mentioning

confidence: 55%

Coronary angioplasty: an end to early closing?

Gullick

Lewanski

1999

Gene Ther

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“…43 This implies that the human VSMC ␣-actin transcriptional control regions could have future application in the field of gene therapy.…”

Section: Lineages Assayed Include Vsmcs (Rabbit and Rat) Hepatocytesmentioning

confidence: 99%

Tissue-selective expression of dominant-negative proteins for the regulation of vascular smooth muscle cell proliferation

Cited by 12 publications

References 42 publications

Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c- myb After Angioplasty of Porcine Coronary Arteries

Localization of c-Myb and Induction of Apoptosis by Antisense Oligonucleotide c- myb After Angioplasty of Porcine Coronary Arteries

Coronary angioplasty: an end to early closing?

Design of a muscle cell-specific expression vector utilising human vascular smooth muscle α-actin regulatory elements

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