The research team led by Professor Wang Guixue of the School of Bioengineering of Chongqing University used zebrafish model biology to study the mechanical regulation mechanism in the process of cardiovascular remodeling, and discovered that hemodynamically induced vascular pruning played a key role in the remodeling of zebrafish tail vein capillary plexus into large vessels. They further revealed the mechanism of hemodynamic -klf6a-tagln2 signal axis regulating vascular pruning of tail vein. The research findings of the team were published in PLoS Genetics, a Nature Index journal, on July 28, 2021.
The original vascular network plexus is formed through angiogenesis, and then go through vascular pruning and other processes to form a vascular network structure with functions and branches. Hemodynamic induced endothelial cell rearrangement plays a key role in vascular pruning, including hemodynamic induced endothelial cell migration and polarity, and cytoskeleton rearrangement. Hemodynamically induced vascular remodeling dysfunction will usually lead to arteriovenous malformations. At present, the role and molecular mechanism of hemodynamics in vascular pruning are still not clear. Exploring the role of hemodynamics in vascular pruning and its molecular mechanism will provide a theoretical basis for further understanding the vascular diseases caused by vascular remodeling disorders.
During the study, the researchers utilized transgenic zebrafish technology in combination with microscopic imaging for observation, and found that the remodeling of ventral capillaries of tail vein plexus of zebrafish embryo into large vessels of tail vein was a hemodynamically induced vascular pruning process. Through real-time dynamic monitoring of the pruning of vein vessels in the tail of zebrafish and the dynamic changes of blood flow velocity, it was discovered that there were hemodynamic differences between the two adjacent vessels, and the vessels with high blood flow velocity were retained. On the contrary, the vessels with low blood flow velocity were finally pruned (Fig. 1). It was further found that the mechanical -klf6a-tagln2 signal axis regulated the pruning of zebrafish tail venous plexus by promoting endothelial cell migration and cytoskeleton remodeling.
Prof. Wang Guixue is the corresponding author of the paper. Associate Professor Wang Yeqi is the corresponding co-author. Doctoral candidate Wen Lin, Post-doctor Zhang Tao and Doctor Wang Jinxuan are first authors of the paper. This Project has won substantial support and assistance from Academician Meng Anming of Tsinghua University, Prof. Shuo Lin of University of California, Los Angeles, Researcher Liu Feng of the Institute of Zoology, CAS, Prof. Ju Rong of Sun Yat-Sen University and Nanjing Xinjia Medical Technology Co., Ltd.
The team led by Prof. Wang Guixue has been concentrating efforts on research of biomechanics, mechanical developmental biology and vascular tissue repair of atherosclerotic cardio cerebrovascular injury, utilizing resources of Key Laboratory of Biorheological Science and Technology, Ministry of Education, National Joint Engineering Laboratory for Vascular Implant Development and other platforms of Chongqing University. In the past 5 years, Prof. Wang Guixue’s team has been engaged in research of neurovascular coupling, vascular biomechanics and tissue repair materials, nano drug therapy of atherosclerotic cardiovascular disease in collaboration of foreign research teams and made considerable breakthroughs. They have published more than 120 research papers in top international journals, including Nature Neuroscience, Advanced Science, Bioactive Materials, and Journal of Biomechanics. Furthermore, their innovation achievements have been well received and referred to by a number of professors from Cambridge University, King's College London, University of Zurich, Stanford University, Harvard University, Massachusetts Institute of Technology, Peking University, Zhejiang University and Macau University. Prof. Wang Guixue was among the list of Highly Cited Chinese Researchers published by Elsevier (biomedical engineering) in both 2019 and 2020.
This Project has been supported by the Key Projects under National Natural Science Foundation (12032007), General Program (11572064, 31771599) and the Natural Science Foundation of Chongqing (cstc2020jcyj-bsh0024).
Different blood flow velocity and endothelial cell rearrangement of two branch vessels during vascular pruning
Information on the paper:
Wen L, Zhang T, Wang J, Jin X, Rouf MA, Luo D, Zhu Y, Lei D, Gregersen H, Wang Y, Wang G. The blood flow-klf6a-tagln2 axis drives vessel pruning in zebrafish by regulating endothelial cell rearrangement and actin cytoskeleton dynamics. PLoS Genet. 2021 Jul 28;17(7):e1009690. doi: 10.1371/journal.pgen.1009690.
Link of the paper:
https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1009690
