Gene therapy with vascular endothelial growth factors

2009 ◽  
Vol 37 (6) ◽  
pp. 1198-1200 ◽  
Author(s):  
Seppo Ylä-Herttuala
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Therapeutic Angiogenesis ◽  
Current Status ◽  
Vascular Endothelial Growth Factors ◽  
Preclinical Studies ◽  
Vascular Endothelial ◽  
Vascular Growth ◽  
Peripheral Ischaemia ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors

Therapeutic angiogenesis is a promising new concept for the treatment of myocardial and peripheral ischaemia. Members of the VEGF (vascular endothelial growth factor) family are among the most powerful modulators of angiogenesis. They regulate vascular growth and maintenance during embryogenesis and in adults. The present review summarizes the current status of therapeutic angiogenesis using VEGF, with special reference to preclinical studies.

scholarly journals The role of vascular endothelial growth factor in the regulation of development and functioning of the brain: new target molecules for pharmacotherapy

2016 ◽  
Vol 62 (2) ◽  
pp. 124-133 ◽  
Author(s):  
V.V. Roslavtceva ◽  
A.B. Salmina ◽  
S.V. Prokopenko ◽  
E.A. Pozhilenkova ◽  
I.V. Kobanenko ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Neurological Diseases ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Vegf Signaling ◽  
Target Molecules ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors ◽  
The Brain

Vascular endothelial growth factors (VEGFs) have been shown to participate in atherosclerosis, arteriogenesis, cerebral edema, neuroprotection, neurogenesis, angiogenesis, postischemic brain and vessel repair. Most of these actions involve VEGF-A and the VEGFR-2 receptor. VEGF signaling pathways represent an important potential for treatment of neurological diseases affecting the brain

Abstract 1066: Ultrasound-targeted Plasmid Delivery of Vascular Endothelial Growth Factor and Angiopoietin-1: Combination Gene Therapy for Therapeutic Angiogenesis

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Alexandra H Smith ◽  
Michael A Kuliszewski ◽  
Hiroko Fujii ◽  
Duncan J Stewart ◽  
Jonathan R Lindner ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Plasmid Dna ◽  
Therapeutic Angiogenesis ◽  
Blood Velocity ◽  
Control Group ◽  
List Type ◽  
Vascular Endothelial ◽  
Time Points ◽  
Endothelial Growth Factor

We have previously shown that ultrasound-mediated (UM) delivery of vascular endothelial growth factor (VEGF) plasmid-bearing microbubbles promotes therapeutic angiogenesis. While VEGF is important during the initiation of angiogenesis, it results in primarily immature vessels, which are prone to late regression. Angiopoietin (Ang)-1 is a potent growth factor that acts to stabilize the neovasculature, later in the angiogenic process. We hypothesized that temporal delivery of VEGF and Ang-1 plasmid DNA would result in a more sustained angiogenic response, as compared to VEGF alone, in the setting of severe chronic ischemia. Methods : Unilateral hindlimb ischemia was produced by iliac artery ligation in 30 rats. At day 14 post-ligation, microvascular blood velocity (β) and flow (MBF) in the proximal hindlimb muscles were assessed by contrast-enhanced ultrasound (CEU). UM-delivery of plasmid (500 μg cDNA)-bearing microbubbles (1×109), was then performed at pre-specified time points, with treatment groups including VEGF alone at day 14; VEGF at day 14 followed by Ang-1 at day 28; and control rats receiving no therapy (n=10 per group). β and MBF were re-assessed at day 28 and 8 wks post-ligation. Results : Relative MBF (normalized to the contralateral normal leg) remained reduced at all time points after ligation in the control group. In VEGF-alone treated animals, MBF in the ischemic leg increased 2 wks after delivery (0.48 ± 0.19 to 0.82 ± 0.23, p < 0.001), but regressed over the next 4 wks (0.61 ± 0.14 at 8 wk, NS vs. 2 wks). In the VEGF/Ang-1 treated animals, MBF in the ischemic leg also increased 2 weeks after VEGF delivery (0.39 ± 0.19 to 0.69 ± 0.28, p < 0.01); however, vascular regression was prevented by late Ang1 delivery (0.83 ± 0.20 at 8 wks, p < 0.005 vs. 2 wks and p<0.01 vs VEGF alone at 8 wks). At week 8, relative β values were greater in VEGF/Ang-1 treated compared to VEGF-alone treated animals (0.87 ± 0.33 to 0.60 ± 0.23, p < 0.05). Conclusions : Compared to delivery of VEGF alone, delivery of Ang-1 plasmid DNA at 2 wks post-VEGF gene delivery results in sustained improvement in MBF, with prevention of late vascular regression. The greater microvascular blood velocity in VEGF/Ang-1 treated muscle may signify improved vascular functionality with late Ang-1 therapy.

Twenty-four-month outcomes of inflammatory choroidal neovascularisation treated with intravitreal anti-vascular endothelial growth factors: a comparison between two treatment regimens

2019 ◽  
Vol 104 (8) ◽  
pp. 1052-1056 ◽  
Author(s):  
Alessandro Invernizzi ◽  
Francesco Pichi ◽  
Richard Symes ◽  
Sophia Zagora ◽  
Aniruddha Kishandutt Agarwal ◽  
...  
Keyword(s):  
Choroidal Neovascularisation ◽  
Vascular Endothelial Growth Factors ◽  
Vascular Endothelial ◽  
Treatment Regimens ◽  
Anti Vegf ◽  
Endothelial Growth Factor ◽  
Endothelial Growth Factors ◽  
Established Treatment ◽  
Number Of Injections

Background and aimThere is still no established treatment regimen for eyes with inflammatory choroidal neovascularisation (iCNV) treated with intravitreal anti-vascular endothelial growth factor (VEGF) injections. This study compared the 24-month outcomes of two treatment regimens of anti-VEGF injections in eyes with iCNV.MethodsEyes with iCNV treated with anti-VEGF injections were divided into two groups: eyes treated with a loading phase of 3 monthly injections and then re-treated as needed (LOADING group) and eyes treated as needed from the beginning (PRN group). Visual acuity (VA), number of injections and iCNV recurrences at 24 months were compared between the groups.ResultsEighty-two eyes were included, 42 in the LOADING and 40 in the PRN group. Baseline VA (mean(SD)) was 57.3 (15.8) letters in the LOADING vs 60.7 (15.6) letters in the PRN group (p=0.32). The VA (mean (95% CI)) increased at 3 months (+14.8 (10.6 to 18.9) and +11.2 (6.4 to 16) letters in the LOADING and PRN group, respectively) and remained significantly higher than baseline over the entire follow-up in both groups (all p<0.001). At 24 months, there was no difference in VA between the LOADING and PRN group (72.3 (14.0) vs 74.7 (11.3) letters, p=0.36) but the LOADING group received significantly more injections (median (Q1–Q3)) than the PRN (4.5 (3–7) vs 2.5 (2–3.2), p<0.0001). The iCNV recurrences were similar in both groups.ConclusionsiCNV responded well to anti-VEGF with significant and sustained VA improvement. The loading phase did not confer any advantage in terms of outcomes. PRN regimen from the beginning was as effective as more intensive treatment.

scholarly journals Implications of Vascular Endothelial Growth Factor for Postischemic Neurovascular Remodeling

2009 ◽  
Vol 29 (10) ◽  
pp. 1620-1643 ◽  
Author(s):  
Dirk Matthias Hermann ◽  
Anil Zechariah
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Brain Plasticity ◽  
Brain Perfusion ◽  
Therapeutic Angiogenesis ◽  
Vascular Endothelial ◽  
Neurologic Recovery ◽  
Vessel Growth ◽  
Neurovascular Remodeling ◽  
Endothelial Growth Factor

Neurovascular remodeling has been recently recognized as a promising target for neurologic therapies. Hopes have emerged that, by stimulating vessel growth, it may be possible to stabilize brain perfusion, and at the same time promote neuronal survival, brain plasticity, and neurologic recovery. In this review, we outline the role of vascular endothelial growth factor (VEGF) in the ischemic brain, analyzing how this growth factor contributes to brain remodeling. Studies with therapeutic VEGF administration resulted in quite variable results depending on the route and time point of delivery. Local VEGF administration consistently enhanced neurologic recovery, whereas acute intravenous delivery exacerbated brain infarcts due to enhanced brain edema. Future studies should answer the following questions: (1) whether increased vessel density translates into improvements in blood flow in the hemodynamically compromised brain; (2) how VEGF influences brain plasticity and contributes to motor and nonmotor recovery; (3) what are the actions of VEGF not only in young animals with preserved vasculature, on which previous studies have been conducted, but also in aged animals and in animals with preexisting atherosclerosis; and (4) whether the effects of VEGF can be mimicked by pharmacological compounds or by cell-based therapies. Only on the basis of such information can more definite conclusions be made with regard to whether the translation of therapeutic angiogenesis into clinics is promising.

scholarly journals Hyperoxia disrupts vascular endothelial growth factor-nitric oxide signaling and decreases growth of endothelial colony-forming cells from preterm infants

2009 ◽  
Vol 297 (6) ◽  
pp. L1160-L1169 ◽  
Author(s):  
Hideshi Fujinaga ◽  
Christopher D. Baker ◽  
Sharon L. Ryan ◽  
Neil E. Markham ◽  
Gregory J. Seedorf ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Vascular Endothelial Growth Factor ◽  
Preterm Infants ◽  
No Production ◽  
Vascular Endothelial ◽  
Enos Expression ◽  
Vascular Growth ◽  
Endothelial Colony Forming Cells ◽  
No Signaling ◽  
Endothelial Growth Factor

Exposure of preterm infants to hyperoxia impairs vascular growth, contributing to the development of bronchopulmonary dysplasia and retinopathy of prematurity. Disruption of vascular endothelial growth factor (VEGF)-nitric oxide (NO) signaling impairs vascular growth. Endothelial progenitor cells (EPCs) may play an important role in vascular growth. Endothelial colony-forming cells (ECFCs), a type of EPC, from human preterm cord blood are more susceptible to hyperoxia-induced growth impairment than term ECFCs. Therefore, we hypothesized that hyperoxia disrupts VEGF-NO signaling and impairs growth in preterm ECFCs and that exogenous VEGF or NO preserves growth in hyperoxia. Growth kinetics of preterm cord blood-derived ECFCs (gestational ages, 27–34 wk) were assessed in room air (RA) and hyperoxia (40–50% oxygen) with or without VEGF, NO, or Nω-nitro-l-arginine. VEGF, VEGF receptor-2 (VEGFR-2), and endothelial NO synthase (eNOS) protein expression and NO production were compared. Compared with RA controls, hyperoxia significantly decreased growth, VEGFR-2 and eNOS expression, and NO production. VEGF treatment restored growth in hyperoxia to values measured in RA controls and significantly increased eNOS expression in hyperoxia. NO treatment also increased growth in hyperoxia. Nω-nitro-l-arginine treatment inhibited VEGF-augmented growth in RA and hyperoxia. We conclude that hyperoxia decreases growth and disrupts VEGF-NO signaling in human preterm ECFCs. VEGF treatment restores growth in hyperoxia by increasing NO production. NO treatment also increases growth during hyperoxia. Exogenous VEGF or NO may protect preterm ECFCs from the adverse effects of hyperoxia and preservation of ECFC function may improve outcomes of preterm infants.

scholarly journals Site-specific therapeutic angiogenesis after systemic administration of vascular endothelial growth factor

1995 ◽  
Vol 21 (2) ◽  
pp. 314-325 ◽  
Author(s):  
Christophe Bauters ◽  
Takayuki Asahara ◽  
Lu P. Zheng ◽  
Satoshi Takeshita ◽  
Stuart Bunting ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Therapeutic Angiogenesis ◽  
Systemic Administration ◽  
Vascular Endothelial ◽  
Site Specific ◽  
Endothelial Growth Factor
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