Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes
- PMID: 12087065
- DOI: 10.1096/fj.01-1042com
Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes
Abstract
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.
Similar articles
-
VEGF-D is the strongest angiogenic and lymphangiogenic effector among VEGFs delivered into skeletal muscle via adenoviruses.Circ Res. 2003 May 30;92(10):1098-106. doi: 10.1161/01.RES.0000073584.46059.E3. Epub 2003 Apr 24. Circ Res. 2003. PMID: 12714562
-
Vascular endothelial growth factors C and D and their VEGFR-2 and 3 receptors in blood and lymphatic vessels in healthy and arthritic synovium.J Rheumatol. 2002 Jan;29(1):39-45. J Rheumatol. 2002. PMID: 11824969
-
Lymphatic versus blood vascular endothelial growth factors and receptors in humans.Microsc Res Tech. 2001 Oct 15;55(2):108-21. doi: 10.1002/jemt.1162. Microsc Res Tech. 2001. PMID: 11596156 Review.
-
Signalling via vascular endothelial growth factor receptor-3 is sufficient for lymphangiogenesis in transgenic mice.EMBO J. 2001 Mar 15;20(6):1223-31. doi: 10.1093/emboj/20.6.1223. EMBO J. 2001. PMID: 11250889 Free PMC article.
-
[Lymphangiogenesis and biological activity ov vascular endothelial growth factor-C].J Soc Biol. 1999;193(2):159-63. J Soc Biol. 1999. PMID: 10451350 Review. French.
Cited by
-
In Vitro Comparison of Lymphangiogenic Potential of Hypoxia Preconditioned Serum (HPS) and Platelet-Rich Plasma (PRP).Int J Mol Sci. 2023 Jan 19;24(3):1961. doi: 10.3390/ijms24031961. Int J Mol Sci. 2023. PMID: 36768283 Free PMC article.
-
TGF-β1 mediates pathologic changes of secondary lymphedema by promoting fibrosis and inflammation.Clin Transl Med. 2022 Jun;12(6):e758. doi: 10.1002/ctm2.758. Clin Transl Med. 2022. PMID: 35652284 Free PMC article.
-
The Protective Role of pVHL in Imiquimod-Induced Psoriasis-like Skin Inflammation.Int J Mol Sci. 2022 May 7;23(9):5226. doi: 10.3390/ijms23095226. Int J Mol Sci. 2022. PMID: 35563616 Free PMC article.
-
Lymphatic Tissue Bioengineering for the Treatment of Postsurgical Lymphedema.Bioengineering (Basel). 2022 Apr 6;9(4):162. doi: 10.3390/bioengineering9040162. Bioengineering (Basel). 2022. PMID: 35447722 Free PMC article. Review.
-
Current Understanding of Pathological Mechanisms of Lymphedema.Adv Wound Care (New Rochelle). 2022 Jul;11(7):361-373. doi: 10.1089/wound.2021.0041. Epub 2021 Nov 25. Adv Wound Care (New Rochelle). 2022. PMID: 34521256 Free PMC article. Review.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous