Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1

Yidong Wang; Bingruo Wu; Pengfei Lu; Donghong Zhang; Brian Wu; Shweta Varshney; Gonzalo Del Monte-Nieto; Zhenwu Zhuang; Rabab Charafeddine; Adam H. Kramer; Nicolas E. Sibinga; Nikolaos G. Frangogiannis; Richard N. Kitsis; Ralf H. Adams; Kari Alitalo; David J. Sharp; Richard P. Harvey; Pamela Stanley; Bin Zhou

doi:10.1038/s41467-017-00654-w

Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1

Yidong Wang, Bingruo Wu, Pengfei Lu, Donghong Zhang, Brian Wu, Shweta Varshney, Gonzalo Del Monte-Nieto, Zhenwu Zhuang, Rabab Charafeddine, Adam H. Kramer, Nicolas E. Sibinga, Nikolaos G. Frangogiannis, Richard N. Kitsis, Ralf H. Adams, Kari Alitalo, David J. Sharp, Richard P. Harvey, Pamela Stanley, Bin Zhou

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Abstract

Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease.

Original language	English (US)
Article number	578
Journal	Nature communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-017-00654-w
State	Published - Dec 1 2017

ASJC Scopus subject areas

Chemistry(all)
Biochemistry, Genetics and Molecular Biology(all)
General
Physics and Astronomy(all)

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Wang, Y., Wu, B., Lu, P., Zhang, D., Wu, B., Varshney, S., Del Monte-Nieto, G., Zhuang, Z., Charafeddine, R., Kramer, A. H., Sibinga, N. E., Frangogiannis, N. G., Kitsis, R. N., Adams, R. H., Alitalo, K., Sharp, D. J., Harvey, R. P., Stanley, P., & Zhou, B. (2017). Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1. Nature communications, 8(1), [578]. https://doi.org/10.1038/s41467-017-00654-w

Wang, Y, Wu, B , Lu, P, Zhang, D, Wu, B, Varshney, S, Del Monte-Nieto, G, Zhuang, Z, Charafeddine, R, Kramer, AH, Sibinga, NE , Frangogiannis, NG , Kitsis, RN, Adams, RH, Alitalo, K, Sharp, DJ, Harvey, RP, Stanley, P & Zhou, B 2017, 'Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1', Nature communications, vol. 8, no. 1, 578. https://doi.org/10.1038/s41467-017-00654-w

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title = "Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1",

abstract = "Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease.",

author = "Yidong Wang and Bingruo Wu and Pengfei Lu and Donghong Zhang and Brian Wu and Shweta Varshney and {Del Monte-Nieto}, Gonzalo and Zhenwu Zhuang and Rabab Charafeddine and Kramer, {Adam H.} and Sibinga, {Nicolas E.} and Frangogiannis, {Nikolaos G.} and Kitsis, {Richard N.} and Adams, {Ralf H.} and Kari Alitalo and Sharp, {David J.} and Harvey, {Richard P.} and Pamela Stanley and Bin Zhou",

note = "Funding Information: We thank W. Lui for assistance with embryonic coronary arteriography. This work was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute R01HL116997 and R01HL133120 (B.Z.), and the National Institute for General Medical Sciences R01GM106417 and the Albert Einstein Cancer Center grant NCI P0113330 (P. S.). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

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doi = "10.1038/s41467-017-00654-w",

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AU - Wang, Yidong

AU - Wu, Bingruo

AU - Lu, Pengfei

AU - Zhang, Donghong

AU - Wu, Brian

AU - Varshney, Shweta

AU - Del Monte-Nieto, Gonzalo

AU - Zhuang, Zhenwu

AU - Charafeddine, Rabab

AU - Kramer, Adam H.

AU - Sibinga, Nicolas E.

AU - Frangogiannis, Nikolaos G.

AU - Kitsis, Richard N.

AU - Adams, Ralf H.

AU - Alitalo, Kari

AU - Sharp, David J.

AU - Harvey, Richard P.

AU - Stanley, Pamela

AU - Zhou, Bin

N1 - Funding Information: We thank W. Lui for assistance with embryonic coronary arteriography. This work was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute R01HL116997 and R01HL133120 (B.Z.), and the National Institute for General Medical Sciences R01GM106417 and the Albert Einstein Cancer Center grant NCI P0113330 (P. S.). Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease.

AB - Coronary artery anomalies may cause life-threatening cardiac complications; however, developmental mechanisms underpinning coronary artery formation remain ill-defined. Here we identify an angiogenic cell population for coronary artery formation in mice. Regulated by a DLL4/NOTCH1/VEGFA/VEGFR2 signaling axis, these angiogenic cells generate mature coronary arteries. The NOTCH modulator POFUT1 critically regulates this signaling axis. POFUT1 inactivation disrupts signaling events and results in excessive angiogenic cell proliferation and plexus formation, leading to anomalous coronary arteries, myocardial infarction and heart failure. Simultaneous VEGFR2 inactivation fully rescues these defects. These findings show that dysregulated angiogenic precursors link coronary anomalies to ischemic heart disease.

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Uncontrolled angiogenic precursor expansion causes coronary artery anomalies in mice lacking Pofut1

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