Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries

Bhardwaj, Shalini; Roy, Himadri; Kärpänen, Terhi; Hi, Yoon; Jauhiainen, Suvi; Hedman, Marja; Alitalo, Kari; Ylä‐Herttuala, Seppo

doi:10.1038/sj.gt.3302426

Cited by 16 publications

(13 citation statements)

References 33 publications

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“…The authors have also recently studied the effects of adventitial angiogenesis on neointima formation in Angiopoietin‐1 transduced arteries. However, Angiopoietin‐1 mediated angiogenesis in the adventitia did not promote neointima formation [13]. A possible explanation for the difference could be that Angiopoietin‐1 has anti‐inflammatory properties [23] and Angiopoietin‐1 signals via a different receptor system than VEGFs.…”

Section: Discussionmentioning

confidence: 99%

“…Periadventitial gene transfer has been used in preclinical and clinical studies for therapeutic angiogeneis, to inhibit neointima formation and to improve vein graft survival [12]. Perivascular collars or sheaths, needle injection catheters and biodegradable gels have been used to deliver vectors to the adventitia [13]. Collar technique has been used as a model to induce intimal hyperplasia.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries

Bhardwaj

Roy

Heikura

et al. 2005

Eur J Clin Investigation

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries

Bhardwaj

Roy

Heikura

et al. 2005

Eur J Clin Investigation

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“…Adenoviral vectors encoding sVEGFR-1-IgG (immunoglobulin) fusion protein (AdsVEGFR-1), [27][28][29] sVEGFR-3-IgG fusion protein (AdsVEGFR-3), 30,31 soluble Tie1-IgG (AdsTie1), soluble Tie2-IgG (AdsTie2) 32, and LacZ (AdLacZ) as a control vector were used for the study. Replication-deficient E1-E3-deleted clinical good manufacturing practice (GMP)-grade adenoviruses were produced in 293T cells.…”

Section: Viral Vectorsmentioning

confidence: 99%

Cotargeting of VEGFR-1 and -3 and angiopoietin receptor Tie2 reduces the growth of solid human ovarian cancer in mice

et al. 2010

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Despite optimal surgery and chemotherapy, the prognosis of ovarian cancer patients remains poor and new treatments are urgently needed. Solid tumors require the formation of new vessels for growth and metastasis. In the present study, we have used soluble vascular endothelial growth factor (sVEGF) receptors sVEGFR-1 and -3, soluble receptors Tie1 and Tie2 and their combinations in an ovarian cancer xenograft model. Human ovarian cancer cells were injected intraperitoneally into nude mice (n ¼ 42) and magnetic resonance imaging (MRI) was used for confirming tumors before gene delivery. Treatment with combined AdsVEGFR-1, AdsVEGFR-3 and AdsTie2 significantly decreased the size of the intraperitoneal tumors compared with the controls (AdLacZ; P ¼ 0.038) with significantly less microvessels and vascular area. Unexpectedly, treatment with combined AdsTie1 and AdsTie2 led to a dramatic shortening of the survival which was not observed in the groups receiving either of the soluble receptors alone (P ¼ 0.031). The only difference to other treatments was liver toxicity observed after the combined Tie receptor treatment.In conclusion, combined inhibition of VEGFR-1, VEGFR-3 and Tie2 pathways was safe and provided efficient therapy for ovarian cancer in mice.

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“…Gene transfer of ANG-1 has been shown to promote robust angiogenesis in ischemic tissues (16)(17)(18). Surprisingly, ANG-1 has recently been implicated in the inhibition of pathologic vascular expansion via its effect on vessel maturation (19)(20)(21).…”

Section: Introductionmentioning

confidence: 99%

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

Shim

Wong

2007

Molecular Cancer Research

152

111

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Angiopoietins (ANG-1 and ANG-2) and their TIE-2 receptor tyrosine kinase have wide-ranging effects on tumor malignancy that includes angiogenesis, inflammation, and vascular extravasation. These multifaceted pathways present a valuable opportunity in developing novel inhibition strategies for cancer treatment. However, the regulatory role of ANG-1 and ANG-2 in tumor angiogenesis remains controversial. There is a complex interplay between complementary yet conflicting roles of both the ANGs in shaping the outcome of angiogenesis. Embryonic vascular development suggests that ANG-1 is crucial in engaging interaction between endothelial and perivascular cells. However, recruitment of perivascular cells by ANG-1 has recently been implicated in its antiangiogenic effect on tumor growth. It is becoming clear that TIE-2 signaling may function in a paracrine and autocrine manner directly on tumor cells because the receptor has been increasingly found in tumor cells. In addition, A 5 B 1 and A v B 5 integrins were recently recognized as functional receptors for ANG-1 and ANG-2. Therefore, both the ligands may have wide-ranging functions in cellular activities that affect overall tumor development. Collectively, these TIE-2 -dependent and TIE-2 -independent activities may account for the conflicting findings of ANG-1 and ANG-2 in tumor angiogenesis. These uncertainties have impeded development of a clear strategy to target this important angiogenic pathway. A better understanding of the molecular basis of ANG-1 and ANG-2 activity in the pathophysiologic regulation of angiogenesis may set the stage for novel therapy targeting this pathway. (Mol Cancer Res 2007;5(7):655 -65)

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Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries

Cited by 16 publications

References 33 publications

VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries

VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries

Cotargeting of VEGFR-1 and -3 and angiopoietin receptor Tie2 reduces the growth of solid human ovarian cancer in mice

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

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Periadventitial angiopoietin-1 gene transfer induces angiogenesis in rabbit carotid arteries

Cited by 16 publications

References 33 publications

VEGF‐A, VEGF‐D and VEGF‐DΔNΔC induced intimal hyperplasia in carotid arteries

VEGF‐A, VEGF‐D and VEGF‐DΔNΔC induced intimal hyperplasia in carotid arteries

Cotargeting of VEGFR-1 and -3 and angiopoietin receptor Tie2 reduces the growth of solid human ovarian cancer in mice

Angiopoietin: A TIE(d) Balance in Tumor Angiogenesis

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VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries

VEGF‐A, VEGF‐D and VEGF‐D^ΔNΔC induced intimal hyperplasia in carotid arteries