puc-header

Myocardial Angiopoietin-1 Controls Atrial Chamber Morphogenesis by Spatiotemporal Degradation of Cardiac Jelly

54 Pages Posted: 11 Apr 2018 Sneak Peek Status: Published

See all articles by Kyun Hoo Kim

Kyun Hoo Kim

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering

Yoshikazu Nakaoka

National Cerebral and Cardiovascular Centre - Department of Vascular Physiology

Hellmut G. Augustin

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH) - Division of Vascular Oncology and Metastasis

Gou Young Koh

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering

More...

Abstract

The four-chamber structure of the mammalian heart is established during embryonic development. While key regulators for ventricular development are well-studied, regulatory mechanisms for atrial chamber morphogenesis remain poorly understood. Here, we found that angiopoietin-1 (Angpt1), a vascular maturation factor, is highly and specifically expressed in atrial myocardium during heart development. Loss of myocardial Angpt1 in mouse embryo led to severe impairment in atrial chamber morphogenesis. We revealed that Angpt1 deficiency results in excessive deposition of cardiac jelly, which disturbs coordination between proliferation and remodeling of myocardium, thereby impairing maturation of atrial chambers. Mechanistically, myocardial Angpt1 activates endocardial Tie2 and positively regulates ADAMTS proteases, which is crucial for proper degradation of cardiac jelly. Accordingly, loss of Tie2 also impairs ADAMTS-mediated degradation of cardiac jelly in atrium. Collectively, myocardial Angpt1/endocardial Tie2 signaling in atrium promotes spatiotemporal degradation of cardiac jelly during early cardiac development, and is, therefore, indispensable for atrial chamber morphogenesis.

Suggested Citation

Kim, Kyun Hoo and Nakaoka, Yoshikazu and Augustin, Hellmut G. and Koh, Gou Young, Myocardial Angiopoietin-1 Controls Atrial Chamber Morphogenesis by Spatiotemporal Degradation of Cardiac Jelly (2018). Available at SSRN: https://ssrn.com/abstract=3155846 or http://dx.doi.org/10.2139/ssrn.3155846
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Kyun Hoo Kim

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering

291 Daehak-ro, Yuseong-gu
Daejeon, 305-701
Korea, Republic of (South Korea)

Yoshikazu Nakaoka

National Cerebral and Cardiovascular Centre - Department of Vascular Physiology

Osaka, 565-8565
Japan

Hellmut G. Augustin

Heidelberg Institute for Stem Cell Technology and Experimental Medicine (HI-STEM GmbH) - Division of Vascular Oncology and Metastasis

Im Neuenheimer Feld 280
Heidleberg, 69120
Germany

Gou Young Koh (Contact Author)

Korea Advanced Institute of Science and Technology (KAIST) - Graduate School of Medical Science and Engineering ( email )

291 Daehak-ro, Yuseong-gu
Daejeon, 305-701
Korea, Republic of (South Korea)

Click here to go to Cell.com

Paper statistics

Abstract Views
239
Downloads
16