Lymphatics in the broken heart
Ebba Bråkenhielm, … , Yuguo Chen, Yihai Cao
Ebba Bråkenhielm, … , Yuguo Chen, Yihai Cao
Published October 15, 2021
Citation Information: J Clin Invest. 2021;131(20):e153448. https://doi.org/10.1172/JCI153448.
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Commentary

Lymphatics in the broken heart

Abstract

Cardiac lymphatics have emerged as a therapeutic target in cardiovascular diseases to limit myocardial edema and inflammation, notably after myocardial infarction (MI). While most experimental therapeutic approaches have focused on vascular endothelial growth factor C (VEGF-C) delivery, it remains uncertain to what degree the beneficial cardiac effects are related to lymphatic expansion in the heart. In this issue of the JCI, Keller, Lim, et al. reexamined the acute functional impact of endogenous cardiac lymphangiogenesis in the infarct zone after MI in mice. Their data, obtained by elegant comparisons of several complementary genetic mouse models, indicate that infarct expansion and left ventricular dilation and function after MI are unaffected by infarct lymphangiogenesis. This Commentary places the results into the context of previous findings. We believe these data will help further advance the research field of cardiac lymphatics to guide better clinical translation and benefit patients with ischemic heart disease.

Authors

Ebba Bråkenhielm, Yuguo Chen, Yihai Cao

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Figure 1

Impact of the VEGF-C/VEGF-D/VEGFR3 axis on cardiac lymphangiogenesis.

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Impact of the VEGF-C/VEGF-D/VEGFR3 axis on cardiac lymphangiogenesis. Ca...
Cardiac lymphangiogenesis is reactivated, notably in the infarct zone, after myocardial infarction (MI). It is mainly regulated by binding of the growth factors VEGF-C and VEGF-D to the plasma membrane–spanning (PM-spanning) VEGFR3 tyrosine kinase (TK) receptor selectively expressed on lymphatic endothelial cells. This signaling leads to expansion of the preexisting lymphatic network in the heart, which, by modulating infarct scar maturation through accelerated resolution of edema and inflammation, may reduce cardiac dysfunction and development of heart failure. However, Keller, Lim, et al. reveal that inactivation of VEGF-C/VEGF-D/VEGFR3–induced infarct lymphangiogenesis had no functional effect on either infarct size or cardiac function 14 days after MI in mice. These data call into question the functionality of infarct lymphatics, because although myocardial edema tended to increase, there was no change in infarct macrophage density following deletion of VEGFR3.