Effect of simulated microgravity induced PI3K-nos2b signalling on zebrafish cardiovascular plexus network formation

Xiang Xie; Daoxi Lei; Qian Zhang; Yeqi Wang; Lin Wen; Zhiyi Ye; Ahmad Ud Din; Dongyu Jia; Antonio Apicella; Guixue Wang

doi:10.1016/j.jbiomech.2019.02.019

Effect of simulated microgravity induced PI3K-nos2b signalling on zebrafish cardiovascular plexus network formation

J Biomech. 2019 Apr 18:87:83-92. doi: 10.1016/j.jbiomech.2019.02.019. Epub 2019 Feb 28.

Authors

Xiang Xie¹, Daoxi Lei², Qian Zhang², Yeqi Wang², Lin Wen², Zhiyi Ye², Ahmad Ud Din², Dongyu Jia³, Antonio Apicella⁴, Guixue Wang⁵

Affiliations

¹ Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China; The School of Basic Medical Sciences, Southwest Medical University, Luzhou, Sichuan Province 646000, China.
² Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China.
³ Department of Biology, Georgia Southern University, Statesboro, GA 30460, USA.
⁴ Advanced Materials Lab, Polytechnic and Base Science School of University of Campania, San Lorenzo, 81031, Italy.
⁵ Key Laboratory of Biorheological and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic address: wanggx@cqu.edu.cn.

PMID: 30850176
DOI: 10.1016/j.jbiomech.2019.02.019

Abstract

Local abnormal angiogenesis and cardiovascular system reorganization have been observed in embryos exposed to a simulated microgravity (SM) environment. In this study, changes in key molecular signals and pathways in cardiovascular development have been investigated under microgravity conditions. In particular, the caudal vein plexus (CVP) network, formed by sprouting angiogenesis has been chosen. Zebrafish embryos were exposed to SM using a ground-based microgravity bioreactor for 24 and 36 h. The SM was observed to have no effect on the zebrafish length, tail width and incubation time whereas it was observed to significantly reduce the heart rate frequency and to promote abnormal development of the CVP network in the embryos. Nitric oxide (NO) content demonstrated that the total proteins in zebrafish embryos were significantly higher in SM than in the control group grown under normal conditions. It was then preliminarily determined how NO signals were involved in SM regulated zebrafish CVP network formation. nos2b MO was injected and CVP network evolution was observed in 36 h post fertilization (hpf) under SM condition. The results showed that the CVP network formation was considerably decreased in the nos2b MO treated group. However, this inhibition of the CVP network development was not observed in control MO group, indicating that nos2b is involved in the SM-regulated vascular development process in zebrafish. Moreover, specific phosphoinositide 3-kinase (PI3K) inhibitors such as LY294002 were also tested on zebrafish embryos under SM condition. This treatment significantly inhibited the formation of zebrafish CVP network. Furthermore, overexpression of nos2b partly rescued the LY294002-caused CVP network failure. Therefore, it can be concluded that SM affects zebrafish CVP network remodeling by enhancing angiogenesis. Additionally, the PI3K-nos2b signaling pathway is involved in this process.

Keywords: CVP network formation; Nos2b; PI3K; Simulated microgravity; Zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Cardiovascular Physiological Phenomena*
Embryo, Nonmammalian
Morphogenesis
Neovascularization, Physiologic* / physiology
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II* / metabolism
Phosphatidylinositol 3-Kinase* / metabolism
Signal Transduction* / physiology
Weightlessness*
Zebrafish* / embryology

Substances

Nitric Oxide
Nitric Oxide Synthase Type II
Phosphatidylinositol 3-Kinase