Vascular Gene Transfer

Kullo, Iftikhar J.; Simari, Robert D.; Schwartz, Robert S.

doi:10.1161/01.atv.19.2.196

Cited by 41 publications

(14 citation statements)

References 184 publications

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“…37,39,40 Adventitial delivery of vectors for gene transfer may be achieved easily in large peripheral arteries by direct application during the surgery. 38 Local overexpression of PAI-1 inhibited progression of type I aneurysms and reduced the degree of adventitial inflammation (Figures 6 and 7). Although PAI-1 inhibited progression of type I aneurysms, there was no effect on type II or III aneurysms (Figure 6c) and also no effect on the degree of vascular wall inflammation.…”

Section: Pai-1 Prevents Aaa Hs Qian Et Almentioning

confidence: 93%

“…36,37 The adventitial also may influence atherosclerosis and vascular hypertrophy secondary to hypertension. 38 Because of the advantages that adventitial gene transfer avoids interruption of blood flow and disruption of the endothelium, as a target for site-specific vascular wall therapy, adventitial-specific gene transfer through the delivery of adenoviral vectors into the peri-arterial sheath has been demonstrated in different animal models. 37,39,40 Adventitial delivery of vectors for gene transfer may be achieved easily in large peripheral arteries by direct application during the surgery.…”

Section: Pai-1 Prevents Aaa Hs Qian Et Almentioning

confidence: 99%

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Overexpression of PAI-1 prevents the development of abdominal aortic aneurysm in mice

Hs¹,

Jm²,

P³

et al. 2007

Gene Ther

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Vessel wall inflammation and matrix destruction are critical to abdominal aortic aneurysm (AAA) formation and rupture. We have previously shown that urokinase plasminogen activator (uPA) is highly expressed in experimental AAA and is essential for AAA formation and expansion. In this study, we examined the effects of overexpression of a natural inhibitor of uPA, plasminogen activator inhibitor-1 (PAI-1), on the development of angiotensin (Ang) II-induced AAA in ApoE-deficient (ApoE À/À ) mice. Mice were treated with recombinant adenovirus containing either the human PAI-1 gene (Ad5.CMV.PAI-1) or the luciferase gene (Ad5.CMV.Luc) delivered either locally by intra-adventitial injection or systemically by tail vein injection. Our results show that local delivery of the PAI-1 gene completely prevented AAA formation (0 vs 55.6% in Ad5.CMV.Luc controls, Po0.05). In contrast, systemic delivery of the PAI-1 gene did not affect AAA incidence (78 vs 90% in Ad5.CMV.Luc controls, P ¼ 0.125). Local delivery of the PAI-1 gene 2 weeks after Ang II infusion prevented further expansion of small aneurysms, but had no significant effect on the progression of larger aneurysms. These data suggest that local PAI-1 gene transfer could be used to stabilize small AAA and reduce the rate of expansion and risk of rupture.

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Section: Pai-1 Prevents Aaa Hs Qian Et Almentioning

confidence: 93%

Section: Pai-1 Prevents Aaa Hs Qian Et Almentioning

confidence: 99%

Overexpression of PAI-1 prevents the development of abdominal aortic aneurysm in mice

Hs¹,

Jm²,

P³

et al. 2007

Gene Ther

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“…Transgene products may also be secreted locally or into the bloodstream for a systemic effect. 1 In animal models, vascular gene transfer has been used successfully to alter neointimal formation and vasomotor reactivity and to stimulate angiogenesis. 2,3 However, the vast majority of gene therapy protocols is involved in cancer therapy.…”

Section: Introductionmentioning

confidence: 99%

Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

et al. 2000

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“…1,2 First-generation adenoviral (FG-Ad) vectors are the most commonly used vectors for vascular gene transfer. Advantages of FG-Ad vectors include an ability to confer high-level transgene expression after only brief contact with vascular tissue and to transfer genes to the (generally) nondividing endothelial and smooth muscle cells of the blood vessel wall.…”

mentioning

confidence: 99%

Improved Vascular Gene Transfer With a Helper-Dependent Adenoviral Vector

et al. 2004

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Background— Adenoviral vectors are the most widely used agents for vascular gene transfer. However, the utility of adenoviral vectors for vascular gene transfer is limited by brevity of expression and by the induction of a significant host inflammatory response. Third-generation or “helper-dependent” adenoviral vectors have achieved prolonged recombinant gene expression in liver and muscle with minimal associated inflammation; however, they have never been tested for vascular gene transfer. Methods and Results— We constructed a helper-dependent adenoviral vector expressing rabbit urokinase plasminogen activator (HD-AduPA). HD-AduPA was compared, in a rabbit model of carotid gene transfer, with a first-generation adenovirus, also expressing rabbit uPA (FG-AduPA). uPA expression and vector DNA were measured in arteries harvested from 3 to 56 days after gene transfer. Vector-specific mRNA, vascular inflammation, and neointimal formation were assessed 14 days after gene transfer. uPA expression was lost, and vector DNA declined rapidly in arteries infused with FG-AduPA. In contrast, uPA expression and vector DNA persisted in HD-AduPA arteries for ≥56 days, with stable expression from 14 to 56 days. Increased uPA expression in HD-AduPA arteries was accompanied by high levels of vector-specific uPA mRNA. Moreover, HD-AduPA arteries had significantly less inflammation and neointimal formation than FG-AduPA arteries. Conclusions— Helper-dependent adenoviral vectors can stably express a therapeutic gene in the vascular wall for ≥8 weeks, with minimal associated inflammation. Helper-dependent adenoviral vectors will be useful agents for vascular gene transfer and gene therapy.

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Vascular Gene Transfer

Cited by 41 publications

References 184 publications

Overexpression of PAI-1 prevents the development of abdominal aortic aneurysm in mice

Overexpression of PAI-1 prevents the development of abdominal aortic aneurysm in mice

Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

Improved Vascular Gene Transfer With a Helper-Dependent Adenoviral Vector

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