@article {893,
	title = {Biomass-derived Lignin Nanoparticles for the Sustained Delivery of Vascular Endothelial Growth Factor-C},
	journal = {Molecular Pharmaceutics},
	year = {Submitted},
	chapter = {submitted/preprint},
	doi = {10.1101/2025.04.23.649697},
	url = {https://doi.org/10.1101/2025.04.23.649697},
	author = {Mavali-Zadeh, Ahmad and Gatto, Emanuela and Lettieri, Raffaella and Bokharaie, Bokharaie and Caravella, Alice and D{\textquoteright}Ottavi, Cadia and di Bartolomeo, Elisabetta and Domenici, Fabio and Sima, Setareh and Correia, Alexandra and Rauniyar, Khushbu and Klose, Anna and Gounani, Zahra and Laaksonen, Timo and K{\"u}nnapuu, Jaana and Jeltsch, Michael}
}
@article {505,
	title = {Ischemia-Reperfusion Injury Enhances Lymphatic Endothelial VEGFR3 and Rejection in Cardiac Allografts},
	journal = {American Journal of Transplantation},
	volume = {16},
	year = {2015},
	month = {12/2015},
	pages = {1160-1172},
	abstract = {Organ damage and innate immunity during heart transplantation may evoke adaptive immunity with serious consequences. Because lymphatic vessels bridge innate and adaptive immunity, they are critical in immune surveillance; however, their role in ischemia{\textendash}reperfusion injury (IRI) in allotransplantation remains unknown. We investigated whether the lymphangiogenic VEGF-C/VEGFR3 pathway during cardiac allograft IRI regulates organ damage and subsequent interplay between innate and adaptive immunity. We found that cardiac allograft IRI, within hours, increased graft VEGF-C expression and lymphatic vessel activation in the form of increased lymphatic VEGFR3 and adhesion protein expression. Pharmacological VEGF-C/VEGFR3 stimulation resulted in early lymphatic activation and later increase in allograft inflammation. In contrast, pharmacological VEGF-C/VEGFR3 inhibition during cardiac allograft IRI decreased early lymphatic vessel activation with subsequent dampening of acute and chronic rejection. Genetic deletion of VEGFR3 specifically in the lymphatics of the transplanted heart recapitulated the survival effect achieved by pharmacological VEGF-C/VEGFR3 inhibition. Our results suggest that tissue damage rapidly changes lymphatic vessel phenotype, which, in turn, may shape the interplay of innate and adaptive immunity. Importantly, VEGF-C/VEGFR3 inhibition during solid organ transplant IRI could be used as lymphatic-targeted immunomodulatory therapy to prevent acute and chronic rejection.},
	doi = {10.1111/ajt.13564},
	url = {http://onlinelibrary.wiley.com/doi/10.1111/ajt.13564/abstract},
	author = {Dashkevich, A. and Raissadati, A. and Syrj{\"a}l{\"a}, S. O. and Zarkada, G. and Ker{\"a}nen, M. A. I. and Tuuminen, R. and Krebs, R. and Anisimov, A. and Jeltsch, M. and Lepp{\"a}nen, V.-M. and Alitalo, K. and Nyk{\"a}nen, A. I. and Lemstr{\"o}m, K. B.}
}
@article {424,
	title = {Vascular endothelial growth factor-angiopoietin chimera with improved properties for therapeutic angiogenesis},
	journal = {Circulation},
	volume = {127},
	year = {2013},
	month = {01/2013},
	pages = {424-434},
	chapter = {424},
	abstract = {BACKGROUND:

There is an unmet need for proangiogenic therapeutic molecules for the treatment of tissue ischemia in cardiovascular diseases. However, major inducers of angiogenesis such as vascular endothelial growth factor (VEGF/VEGF-A) have side effects that limit their therapeutic utility in vivo, especially at high concentrations. Angiopoietin-1 has been considered to be a blood vessel stabilization factor that can inhibit the intrinsic property of VEGF to promote vessel leakiness. In this study, we have designed and tested the angiogenic properties of chimeric molecules consisting of receptor-binding parts of VEGF and angiopoietin-1. We aimed at combining the activities of both factors into 1 molecule for easy delivery and expression in target tissues.
METHODS AND RESULTS:

The VEGF-angiopoietin-1 (VA1) chimeric protein bound to both VEGF receptor-2 and Tie2 and induced the activation of both receptors. Detailed analysis of VA1 versus VEGF revealed differences in the kinetics of VEGF receptor-2 activation and endocytosis, downstream kinase activation, and VE-cadherin internalization. The delivery of a VA1 transgene into mouse skeletal muscle led to increased blood flow and enhanced angiogenesis. VA1 was also very efficient in rescuing ischemic limb perfusion. However, VA1 induced less plasma protein leakage and myeloid inflammatory cell recruitment than VEGF. Furthermore, angioma-like structures associated with VEGF expression were not observed with VA1.
CONCLUSIONS:

The VEGF-angiopoietin-1 chimera is a potent angiogenic factor that triggers a novel mode of VEGF receptor-2 activation, promoting less vessel leakiness, less tissue inflammation, and better perfusion in ischemic muscle than VEGF. These properties of VA1 make it an attractive therapeutic tool.},
	author = {Andrey Anisimov and Denis Tvorogov and Annamari Alitalo and Veli-Matti Lepp{\"a}nen and Y An and EC Han and F Orsenigo and EI Ga{\'a}l and Tanja Holopainen and YJ Koh and Tuomas Tammela and P Korpisalo and Salla Keskitalo and Michael Jeltsch and Seppo Yl{\"a}-Herttuala and Elisabetta Dejana and GY Koh and C Choi and Pipsa Saharinen and Kari Alitalo}
}
@article {39,
	title = {Claudin-like protein 24 interacts with the VEGFR-2 and VEGFR-3 pathways and regulates lymphatic vessel development},
	journal = {Genes Dev},
	volume = {24},
	year = {2010},
	month = {2010/May/},
	pages = {875 - 80},
	abstract = {The Claudin-like protein of 24 kDa (CLP24) is a hypoxia-regulated transmembrane protein of unknown function. We show here that clp24 knockdown in Danio rerio and Xenopus laevis results in defective lymphatic development. Targeted disruption of Clp24 in mice led to enlarged lymphatic vessels having an abnormal smooth muscle cell coating. We also show that the Clp24(-/-) phenotype was further aggravated in the Vegfr2(+/LacZ) or Vegfr3(+/LacZ) backgrounds and that CLP24 interacts with vascular endothelial growth factor receptor-2 (VEGFR-2) and VEGFR-3 and attenuates the transcription factor CREB phosphorylation via these receptors. Our results indicate that CLP24 is a novel regulator of VEGFR-2 and VEGFR-3 signaling pathways and of normal lymphatic vessel structure.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/20439428},
	author = {Saharinen, Pipsa and Helotera, Hanna and Miettinen, Juho and Norrmen, Camilla and D{\textquoteright}Amico, Gabriela and Jeltsch, Michael and Langenberg, Tobias and Vandevelde, Wouter and Ny, Annelii and Dewerchin, Mieke and Carmeliet, Peter and Alitalo, Kari}
}
@article {36,
	title = {Reevaluation of the role of VEGF-B suggests a restricted role in the revascularization of the ischemic myocardium},
	journal = {Arterioscler Thromb Vasc Biol},
	volume = {28},
	year = {2008},
	month = {2008/Sep/},
	pages = {1614 - 20},
	abstract = {OBJECTIVE: The endogenous role of the VEGF family member vascular endothelial growth factor-B (VEGF-B) in pathological angiogenesis remains unclear. METHODS AND RESULTS: We studied the role of VEGF-B in various models of pathological angiogenesis using mice lacking VEGF-B (VEGF-B(-/-)) or overexpressing VEGF-B(167). After occlusion of the left coronary artery, VEGF-B deficiency impaired vessel growth in the ischemic myocardium whereas, in wild-type mice, VEGF-B(167) overexpression enhanced revascularization of the infarct and ischemic border zone. By contrast, VEGF-B deficiency did not affect vessel growth in the wounded skin, hypoxic lung, ischemic retina, or ischemic limb. Moreover, VEGF-B(167) overexpression failed to enhance vascular growth in the skin or ischemic limb. CONCLUSIONS: VEGF-B appears to have a relatively restricted angiogenic activity in the ischemic heart. These insights might offer novel therapeutic opportunities.},
	url = {http://view.ncbi.nlm.nih.gov/pubmed/18511699},
	author = {Li, Xuri and Tjwa, Marc and Van Hove, Inge and Enholm, Berndt and Neven, Elke and Paavonen, Karri and Jeltsch, Michael and Juan, Toni Diez and Sievers, Richard E and Chorianopoulos, Emmanuel and Wada, Hiromichi and Vanwildemeersch, Maarten and Noel, Agnes and Foidart, Jean-Michel and Springer, Matthew L and von Degenfeld, Georges and Dewerchin, Mieke and Blau, Helen M and Alitalo, Kari and Eriksson, Ulf and Carmeliet, Peter and Moons, Lieve}
}
