Transgenic Induction of Vascular Endothelial Growth Factor-C Is Strongly Angiogenic in Mouse Embryos but Leads to Persistent Lymphatic Hyperplasia in Adult Tissues

Lohela, Marja; Heloterä, Hanna; Haiko, Paula; Dumont, Daniel; Alitalo, Kari

doi:10.2353/ajpath.2008.080378

Cited by 68 publications

(65 citation statements)

References 53 publications

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“…Historical studies revealed that skin lymphatics induced to grow by chemical irritants can persist for many months after exposure (44). Subsequent experiments confirmed that lymphatic growth resists regression after (a) inflammation resolves (13), (b) growth factor overexpression is switched off (6,45), and (c) genetic deletion of VEGFR-2 and VEGFR-3 (46, 47).…”

Section: Attributes and Limitations Of The Ccsp/vegf-c Mouse Model Ofmentioning

confidence: 79%

Rapamycin reversal of VEGF-C–driven lymphatic anomalies in the respiratory tract

Bałuk¹,

Yao²,

Flores³

et al. 2017

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Section: Attributes and Limitations Of The Ccsp/vegf-c Mouse Model Ofmentioning

confidence: 79%

Rapamycin reversal of VEGF-C–driven lymphatic anomalies in the respiratory tract

Bałuk¹,

Yao²,

Flores³

et al. 2017

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“…VEGFC is well known for its role in lymphangiogenesis (Lohela et al, 2009), but is becoming increasingly appreciated for its effects on blood vasculature (Cao et al, 1998;Lohela et al, 2008; Tammela et al., 2011;Villefranc et al, 2013). VEGFC binds VEGFR3, which is expressed in lymphatic vessels and in embryonic blood endothelial cells (Tammela et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

et al. 2014

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Identifying coronary artery progenitors and their developmental pathways could inspire novel regenerative treatments for heart disease. Multiple sources of coronary vessels have been proposed, including the sinus venosus (SV), endocardium and proepicardium, but their relative contributions to the coronary circulation and the molecular mechanisms regulating their development are poorly understood. We created an ApjCreER mouse line as a lineagetracing tool to map SV-derived vessels onto the heart and compared the resulting lineage pattern with endocardial and proepicardial contributions to the coronary circulation. The data showed a striking compartmentalization to coronary development. ApjCreER-traced vessels contributed to a large number of arteries, capillaries and veins on the dorsal and lateral sides of the heart. By contrast, untraced vessels predominated in the midline of the ventral aspect and ventricular septum, which are vessel populations primarily derived from the endocardium. The proepicardium gave rise to a smaller fraction of vessels spaced relatively uniformly throughout the ventricular walls. Dorsal (SV-derived) and ventral (endocardialderived) coronary vessels developed in response to different growth signals. The absence of VEGFC, which is expressed in the epicardium, dramatically inhibited dorsal and lateral coronary growth but left vessels on the ventral side unaffected. We propose that complementary SV-derived and endocardial-derived migratory routes unite to form the coronary vasculature and that the former requires VEGFC, revealing its role as a tissue-specific mediator of blood endothelial development.

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“…By contrast, a presumptive tyrosine phosphorylation-deficient zebrafish vegfr3 missense mutant shows primary defects in lymphatic development but no angiogenesis defects (Hogan et al, 2009), although the authors of this study suggest that this may reflect 'very low-level, residual signaling in the presence of the I1042S mutation'. Overexpression of Vegfc during early murine development (prior to E16.5) is also highly angiogenic (Lohela et al, 2008). However, targeted inactivation of both known mouse Vegfr3 ligands (Vegfc and Vegfd) does not yield defects in blood vessel development analogous to those caused by loss of Vegfr3 , suggesting that there are Vegfc/d-independent, or redundant, functions for Vegfr3 in murine blood vessel formation.…”

Section: Vegfc/vegfr3 Signaling During Angiogenesismentioning

confidence: 99%

Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3

et al. 2011

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SUMMARYHere, we show that a novel Rspo1-Wnt-Vegfc-Vegfr3 signaling pathway plays an essential role in developmental angiogenesis. A mutation in R-spondin1 (rspo1), a Wnt signaling regulator, was uncovered during a forward-genetic screen for angiogenesisdeficient mutants in the zebrafish. Embryos lacking rspo1 or the proposed rspo1 receptor kremen form primary vessels by vasculogenesis, but are defective in subsequent angiogenesis. Endothelial cell-autonomous inhibition of canonical Wnt signaling also blocks angiogenesis in vivo. The pro-angiogenic effects of Rspo1/Wnt signaling are mediated by Vegfc/Vegfr3(Flt4) signaling. Vegfc expression is dependent on Rspo1 and Wnt, and Vegfc and Vegfr3 are necessary to promote angiogenesis downstream from Rspo1-Wnt. As all of these molecules are expressed by the endothelium during sprouting stages, these results suggest that Rspo1-Wnt-VegfC-Vegfr3 signaling plays a crucial role as an endothelial-autonomous permissive cue for developmental angiogenesis.

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Transgenic Induction of Vascular Endothelial Growth Factor-C Is Strongly Angiogenic in Mouse Embryos but Leads to Persistent Lymphatic Hyperplasia in Adult Tissues

Cited by 68 publications

References 53 publications

Rapamycin reversal of VEGF-C–driven lymphatic anomalies in the respiratory tract

Rapamycin reversal of VEGF-C–driven lymphatic anomalies in the respiratory tract

The sinus venosus contributes to coronary vasculature through VEGFC-stimulated angiogenesis

Rspo1/Wnt signaling promotes angiogenesis via Vegfc/Vegfr3

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