scholarly journals Sulfated polysaccharide directs therapeutic angiogenesis via endogenous VEGF secretion of macrophages

2021 ◽  
Vol 7 (7) ◽  
pp. eabd8217
Author(s):  
Yuanman Yu ◽  
Kai Dai ◽  
Zehua Gao ◽  
Wei Tang ◽  
Tong Shen ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Therapeutic Angiogenesis ◽  
Sulfated Polysaccharide ◽  
Vascular Endothelial ◽  
Ischemic Disease ◽  
Vegfr2 Signaling ◽  
Inflammatory Macrophages ◽  
Endothelial Growth Factor ◽  
Potential Cancer ◽  
Remarkable Progress

Notwithstanding the remarkable progress in the clinical treatment of ischemic disease, proangiogenic drugs mostly suffer from their abnormal angiogenesis and potential cancer risk, and currently, no off-the-shelf biomaterials can efficiently induce angiogenesis. Here, we reported that a semisynthetic sulfated chitosan (SCS) readily engaged anti-inflammatory macrophages and increased its secretion of endogenous vascular endothelial growth factor (VEGF) to induce angiogenesis in ischemia via a VEGF-VEGFR2 signaling pathway. The depletion of host macrophages abrogated VEGF secretion and vascularization in implants, and the inhibition of VEGF or VEGFR2 signaling also disrupted the macrophage-associated angiogenesis. In addition, in a macrophage-inhibited mouse model, SCS efficiently helped to recover the endogenous levels of VEGF and the number of CD31hiEmcnhi vessels in ischemia. Thus, both sulfated group and pentasaccharide sequence in SCS played an important role in directing the therapeutic angiogenesis, indicating that this highly bioactive biomaterial can be harnessed to treat ischemic disease.

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.

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 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

Nanosphere-mediated delivery of vascular endothelial growth factor gene for therapeutic angiogenesis in mouse ischemic limbs

Biomaterials ◽  
2008 ◽  
Vol 29 (8) ◽  
pp. 1109-1117 ◽  
Author(s):  
Sun-Woong Kang ◽  
Hee-Won Lim ◽  
Sang-Woo Seo ◽  
Oju Jeon ◽  
Minhyung Lee ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Therapeutic Angiogenesis ◽  
Vascular Endothelial ◽  
Factor Gene ◽  
Growth Factor Gene ◽  
Endothelial Growth Factor
Sign in / Sign up

Export Citation Format

Share Document