Post-intervention vessel remodeling

Rutanen, Juha; Puhakka, H; Ylä‐Herttuala, Seppo

doi:10.1038/sj.gt.3301866

Cited by 16 publications

(11 citation statements)

References 54 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The selected genes, VEGF, HSP60 and PCNA, are 3 markers often monitored for initiation and progression of vascular pathologies [32,33,34,35,36,37,38,39,40,41]. PCNA is identified as playing an important role in vascular remodeling (proliferation, migration and phenotypic change).…”

Section: Discussionmentioning

confidence: 99%

“…Next, arterial remodeling begins at the injury site, which, similar to the reported expression of VEGF, is sustained. In addition, the implicated roles of VEGF, such as wound healing, neovascularization and endothelial cell migration [40], are pivotal to vascular remodeling. Hence, these parallels corroborate the argument that remodeling is at least partly accomplished through the activation of VEGF.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response

et al. 2009

View full text Add to dashboard Cite

This study addresses whether pathological levels of cyclic strain activate the c-Myc promoter, leading to c-Myc transcription and downstream gene induction in human umbilical vein endothelial cells (HUVEC) or human aortic endothelial cells (HAEC). mRNA and protein expression of c-Myc under physiological (6–10%) and pathological cyclic strain conditions (20%) were studied. Both c-Myc mRNA and protein expression increased 2–3-fold in HUVEC cyclically strained at 20%. c-Myc protein increased 4-fold in HAEC. In HUVEC, expression of mRNA peaked at 1.5–2 h. Subsequently, the effect of modulating c-Myc on potential downstream gene targets was determined. A small molecular weight compound that binds to and stabilizes the silencer element in the c-Myc promoter attenuates cyclic strain-induced c-Myc transcription by about 50%. This compound also modulates c-Myc downstream gene targets that may be instrumental in induction of vascular disease. Cyclic strain-induced gene expression of vascular endothelial growth factor, proliferating cell nuclear antigen and heat shock protein 60 are attenuated by this compound. These results offer a possible mechanism and promising clinical treatment for vascular diseases initiated by increased cyclic strain.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response

et al. 2009

View full text Add to dashboard Cite

show abstract

“…These processes together with the proliferation of SMCs and the accumulation of ECM eventually lead to restenosis [16]. Thus, restenosis is a complex process where interventions simultaneously directed to more than one pathogenetic mechanism could theoretically be more efficient than single treatments [26]. …”

Section: Discussionmentioning

confidence: 99%

Tissue Inhibitor of Metalloproteinase 1 Adenoviral Gene Therapy Alone Is Equally Effective in Reducing Restenosis as Combination Gene Therapy in a Rabbit Restenosis Model

Puhakka¹,

Turunen²,

Rutanen³

et al. 2005

J Vasc Res

View full text Add to dashboard Cite

Neointimal formation is a common feature after angioplasty, bypass grafting and stenting. Angioplasty damages endothelium, causing pathological changes in arteries which lead to smooth muscle cell proliferation, synthesis of extracellular matrix components and eventually restenosis formation. Adenoviruses offer an efficient transgene expression in the vascular system. In this study, we compared the effects of different gene combinations. We wanted to find out whether adenoviral catheter-mediated delivery of an additive combination of the vascular endothelial growth factor (VEGF)-A with VEGF-C is more effective than the combination of tissue inhibitor of metalloproteinase 1 (TIMP-1) alone or with VEGF-C in a rabbit balloon denudation model. Additionally, we wanted to clarify whether the combination therapy prolongs the treatment effect. It was found that TIMP-1 alone prevents restenosis and that the combination of VEGF-A and VEGF-C has a similar effect at the 2-week time point. However, the combination of VEGF-A and VEGF-C lost the treatment effect at the 4-week time point due to the catch-up growth of neointima. On the other hand, TIMP-1 and the combination of TIMP-1 with VEGF-C still had an extended treatment effect at the 4-week time point. When considering the gene combination used in this study, it is concluded that gene therapy with adenoviral TIMP-1 alone is sufficient in reducing restenosis and that combination gene therapy does not bring any significant advantages.

show abstract

“…SOD and CAT recombinant enzyme therapy is limited by the short half-life of both enzymes in the blood stream and their inability to penetrate cells. We therefore proposed to use local adenovirus-mediated gene transfer at the site of angioplasty to provide high concentrations and obtain lasting effects of SOD and CAT [15]. The aim of our study was to evaluate the effect of local adenovirus-mediated gene transfer of SOD and CAT on ROS production, restenosis, remodeling, endothelium, collagen, and inflammation after balloon angioplasty.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-Mediated Gene Transfer of Superoxide Dismutase and Catalase Decreases Restenosis after Balloon Angioplasty

Durand

Zen²,

Addad³

et al. 2005

J Vasc Res

View full text Add to dashboard Cite

Background: Reactive oxygen species (ROS) production increases after injury and potentially contributes to restenosis after angioplasty. We therefore evaluated the effect of adenovirus-mediated gene transfer (Ad) of superoxide dismutase (SOD) and catalase (CAT) on ROS production and restenosis after balloon angioplasty. Methods: O₂^– and H₂O₂production was quantified in cultured cells after incubation with either LPS or CuSO₄. Angioplasty and gene transfer were performed in rabbit atherosclerotic iliac arteries. One artery was injected with AdSOD and AdCAT, while the contralateral artery was injected with an adenovirus carrying no transgene, and served as control. Results: ROS production was significantly decreased after adenovirus-mediated gene transfer of SOD and CAT as compared with control. Treated arteries showed less restenosis (32 ± 27 vs. 63 ± 19%, p = 0.003) and less constrictive remodeling (1.2 ± 0.3 vs. 0.9 ± 0.2, p = 0.02) than control arteries. Arteries injected with AdSOD and AdCAT showed better vasoreactivity to acetylcholine (11 ± 4 vs. –1 ± 6%, p < 0.05), lower collagen density (43 ± 16 vs. 53 ± 23%, p = 0.03), and lower inflammatory cell infiltration (22 ± 6 vs. 36 ± 11%, p = 0.04) than control arteries. Conclusions: Our data suggest that adenovirus-mediated gene transfer of SOD and CAT reduced oxidative stress, restenosis, collagen accumulation, and inflammation and improved endothelial function after angioplasty.

show abstract

Post-intervention vessel remodeling

Cited by 16 publications

References 54 publications

Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response

Modulating the Functional Contributions of c-Myc to the Human Endothelial Cell Cyclic Strain Response

Tissue Inhibitor of Metalloproteinase 1 Adenoviral Gene Therapy Alone Is Equally Effective in Reducing Restenosis as Combination Gene Therapy in a Rabbit Restenosis Model

Adenovirus-Mediated Gene Transfer of Superoxide Dismutase and Catalase Decreases Restenosis after Balloon Angioplasty

Contact Info

Product

Resources

About