Regulation of scar formation by vascular endothelial growth factor

Wilgus, Traci A.; Ferreira, Ahalia M.; Oberyszyn, Tatiana M.; Bergdall, Valerie; DiPietro, Luisa A.

doi:10.1038/labinvest.2008.36

Cited by 276 publications

(250 citation statements)

References 70 publications

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“…This study shows that VEGF has a strong influence in wound healing which upholds the previous studies by Li et al and Wilgus et al [26,39]. Vascular endothelial growth factor also affects a fibroblastic activity in addition to angiogenesis [40].…”

Section: Discussionsupporting

confidence: 90%

Post-trabeculectomy topical bevacizumab preventing bleb failure: a preliminary study

Bhasker

Saxena

Singh

2012

j ocul biol dis inform

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This study aims to evaluate the efficacy and safety of post-trabeculectomy topical bevacizumab, in preventing bleb failure. A total of 11 females and 12 males were enrolled for the study. After a complete ophthalmic evaluation, the patients underwent trabeculectomy. Full ophthalmic examination was done the next day, which included visual acuity, intraocular pressure (IOP), and bleb morphology. Next, two drops of bevacizumab [0.25 mg (0.01 ml)] were instilled over the wound area with a tuberculin (1 ml) syringe. Pressure was applied at the medial canthus to prevent it from going into the lacrimal passage. Similar postoperative procedures were repeated at 1, 2, 3, and 4 weeks. So in all, five instillations of bevacizumab were completed. Later, the patients were followed at 1-month interval for 6 months. Target IOP was achieved in all eyes and was maintained during the study period of 6 months without any anti-glaucoma medication. Average IOP before trabeculectomy was 27.27±8.92 mmHg, which decreased postoperatively to 8.77±0.97 mmHg at 3 months and 9.27±1.16 mmHg at 6 months. This drop in IOP was statistically significant on both occasions (p=0.00). A nice low filtering bleb was formed after the surgery, and it remained the same during the study period. The other parameters like cup-to-disc ratio and visual field did not change during the 6 months of study as expected because glaucoma is a slow progressive disease. Modulating the wound at multiple sites by bevacizumab (inflammation, proliferative, and remodeling stages) can lead to success of trabeculectomy.

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Section: Discussionsupporting

confidence: 90%

Post-trabeculectomy topical bevacizumab preventing bleb failure: a preliminary study

Bhasker

Saxena

Singh

2012

j ocul biol dis inform

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“…Studies of vascular regression in wounds are very likely to have applicability to multiple disease states. The failure of appropriate vascular regression has been implicated in pathological conditions such as cancer, inflammatory diseases like arthritis, some types of chronic wounds, and scarring (19,36,44). In contrast, an overinhibition of angiogenesis is characteristic of many poorly healing wounds, particularly in patients with diabetes (29), and is highly implicated in various cardiovascular diseases (35).…”

Section: Discussionmentioning

confidence: 99%

Sprouty2 downregulates angiogenesis during mouse skin wound healing

Wietecha¹,

Chen²,

Ranzer

et al. 2011

American Journal of Physiology-Heart and Circulatory Physiology

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Angiogenesis is regulated by signals received by receptor tyrosine kinases such as vascular endothelial growth factor receptors. Mammalian Sprouty (Spry) proteins are known to function by specifically antagonizing the activation of the mitogen-activated protein kinase signaling pathway by receptor tyrosine kinases, a pathway known to promote angiogenesis. To examine the role of Spry2 in the regulation of angiogenesis during wound repair, we used a model of murine dermal wound healing. Full-thickness excisional wounds (3 mm) were made on the dorsum of anesthetized adult female FVB mice. Samples were harvested at multiple time points postwounding and analyzed using real-time RT-PCR, Western blot analysis, and immunofluorescent histochemistry. Spry2 mRNA and protein levels in the wound bed increased significantly during the resolving phases of healing, coincident with the onset of vascular regression in this wound model. In another experiment, intracellular levels of Spry2 or its dominant-negative mutant (Y55F) were elevated by a topical application to the wounds of controlled-release gel containing cell permeable, transactivator of transcription-tagged Spry2, Spry2 Y55F , or green fluorescent protein (as control). Wound samples were analyzed for vascularity using CD31 immunofluorescent histochemistry as well as for total and phospho-Erk1/2 protein content. The treatment of wounds with Spry2 resulted in a significant decrease in vascularity and a reduced abundance of phospho-Erk1/2 compared with wounds treated with the green fluorescent protein control. In contrast, the wounds treated with the dominant-negative Spry2 Y55F exhibited a moderate increase in vascularity and elevated phospho-Erk1/2 content. These results indicate that endogenous Spry2 functions to downregulate angiogenesis in the healing murine skin wound, potentially by inhibiting the mitogenactivated protein kinase signaling pathway.

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“…76 Other mediators produced by mast cells, such as PDGF, prostaglandin E 2 , and VEGF have also been shown to promote fibrosis in fetal wounds. 40,77,78 Mast cells can also stimulate scar formation indirectly by stimulating inflammation. Activated mast cells increase the magnitude of inflammation in wounds by enhancing vascular permeability, stimulating endothelial cell adhesion molecule expression, and producing chemokines that attract circulating leukocytes to the wound.…”

Section: Mechanisms Of Mast Cells In Scar Formationmentioning

confidence: 99%