Xiang Xie

In vitro and in vivo investigations on the effects of low-density lipoprotein concentration polarization and haemodynamics on atherosclerotic localization in rabbit and zebrafish

Atherosclerosis (AS) commonly occurs in the regions of the arterial tree with haemodynamic peculiarities, including local flow field disturbances, and formation of swirling flow and vortices. The aim of our study was to confirm low-density lipoprotein (LDL) concentration polarization in the vascular system in vitro and in vivo, and investigate the effects of LDL concentration polarization and flow field alterations on atherosclerotic localization. Red fluorescent LDL was injected into optically transparent Flk1: GFP zebrafish embryos, and the LDL distribution in the vascular lumen was investigated in vivo using laser scanning confocal microscopy. LDL concentration at the vascular luminal surface was found to be higher than that in the bulk. The flow field conditions in blood vessel segments were simulated and measured, and obvious flow field disturbances were found in the regions of vascular geometry change. The LDL concentration at the luminal surface of bifurcation was significantly higher than that in the straight segment, possibly owing to the atherogenic effect of disturbed flow. Additionally, a stenosis model of rabbit carotid arteries was generated. Atherosclerotic plaques were found to have occurred in the stenosis group and were more severe in the stenosis group on a high-fat diet. Our findings provide the first ever definite proof that LDL concentration polarization occurs in the vascular system in vivo. Both lipoprotein concentration polarization and flow field changes are involved in the infiltration/accumulation of atherogenic lipids within the location of arterial luminal surface and promote the development of AS.

High shear stress induces atherosclerotic vulnerable plaque formation through angiogenesis.

Rupture of atherosclerotic plaques causing thrombosis is the main cause of acute coronary syndrome and ischemic strokes. Inhibition of thrombosis is one of the important tasks developing biomedical materials such as intravascular stents and vascular grafts. Shear stress (SS) influences the formation and development of atherosclerosis. The current review focuses on the vulnerable plaques observed in the high shear stress (HSS) regions, which localizes at the proximal region of the plaque intruding into the lumen. The vascular outward remodelling occurs in the HSS region for vascular compensation and that angiogenesis is a critical factor for HSS which induces atherosclerotic vulnerable plaque formation. These results greatly challenge the established belief that low shear stress is important for expansive remodelling, which provides a new perspective for preventing the transition of stable plaques to high-risk atherosclerotic lesions.

Blood Flow Regulates Zebrafish Caudal Vein Plexus Angiogenesis by ERK5-klf2a-nos2b Signaling

BACKGROUND Vascular network formation induced by angiogenesis plays an important role in many physiological and pathological processes. However, the role of blood flow and underlying mechanisms in vascular network formation, for example for the development of the caudal vein plexus (CVP), is poorly understood. OBJECTIVE The aim of this study was to explore the role of ERK5-klf2a-nos2b signaling in the CVP angiogenesis. METHOD AND RESULTS In this study on tnnt2a-MO injection and chemical blood flow modulator treatment in zebrafish embryos, we demonstrated that decreased blood flow disrupted CVP formation. The hemodynamic force was quantitatively analyzed. Furthermore, CVP angiogenesis in zebrafish embryos was inhibited by disruption of the blood flow downstream effectors ERK5, klf2a, and nos2b in response to treatment with the ERK5 specific inhibitor and to injection of klf2a-MO, nos2b-MO. Overexpression of klf2a mRNA or nos2b mRNA restored vascular defects in tnnt2a or klf2a morphants. The data suggest that flow-induced ERK5-klf2a-nos2b signaling is involved in CVP angiogenesis in zebrafish embryos. CONCLUSION We have demonstrated that blood flow is essential for vascular network formation, specifically for CVP angiogenesis in zebrafish. A novel genetic and mechanical mechanism was discovered in which ERK5 facilitates the integration of blood flow with the downstream klf2a-nos2b signaling for CVP angiogenesis.

Erratum to: AAMP Regulates Endothelial Cell Migration and Angiogenesis Through RhoA/Rho Kinase Signaling

Address correspondence to Guixue Wang, Key Laboratory for Biorheological Science and Technology of Ministry of Education (Chongqing University), State and Local Joint Engineering Laboratory For Vascular Implants (Chongqing), Bioengineering College of Chongqing University, Chongqing 400030, China. Electronic mail: guixue_wang@126.com The online version of the original article can be found under doi: 10.1007/s10439-015-1442-0. Annals of Biomedical Engineering, Vol. 44, No. 3, March 2016 ( 2015) pp. 830–832 DOI: 10.1007/s10439-015-1537-7

Effect of horizontal rotary culture on zebrafish vascular development: Effect of horizontal rotary culture on zebrafish vascular development

With the development of space life science, a study on the influence of microgravity on organism has been an increasingly concerned topic. Lots of studies indicate that microgravity plays an important role in the early development of embryos. The vascular system as the first-function system of embryos provides an interesting topic for many researchers. However, those studies were mostly carried out in vitro by rotary cell culture system (RCCS), while few experiments were done in vivo. Using zebrafish as a model, this research investigated the effects of horizontal rotary culture on the vascular development in vivo. Zebrafish embryos at 24 hpf (hour post-fertilization) were selected and divided into two groups. One group was cultured by the shaker, and the other was cultured normally as the control. After 12 h, all the embryos were collected and detected. The phenotype of zebrafish was observed by stereo microscope. Then, the expression of vascular specific expression factor, flk1, flt4, and ephrinB2 was compared by RT-PCR, qPCR, and in situ hybridization, respectively. Cell apoptosis and proliferation in situ were observed using TUNEL assay and bromodeoxyuridine incorporation. The results demonstrated that horizontal rotary culture at 90 r/min decreased the hatching of embryos (10.3±0.41 vs. 0.0, P<0.05), accelerate the heart rate (223.5±2.32 vs. 185.0±3.23, P<0.05) and increased the content of melanin in zebrafish significantly. At the same time, we found some differences in the vascular system of zebrafish after horizontal rotary culture which caused a down regulation of flk1, flt4, and ephrinB2. On the other hand, horizontal rotary culture accelerated the apoptosis of cells in zebrafish, but showed no significance in proliferation. In conclusion, horizontal rotary culture has a significant influence on the vascular development in zebrafish.

Study on Adhesion Force of Endothelial Progenitor Cells and Endothelial Cells on Different Adhesion Substrates

This study was designed to evaluate the adhesion force of endothelial progenitor cells (EPCs) on different substrate materials. The single micropipette aspiration technique was used for measuring the adhesion force of single EPC on the substrate material, including gelatin, antibody VEGFR-2 and antibody CD133. The adhesion force of human umbilical vein endothelial cell (HUVEC/EC) on each substrate material was measured in the control groups. Results showed the adhesion characters of EPCs on the three substrate materials were better than that of HUVECs. And at the same time, the adhesion force of EPCs to antibody CD133 was the strongest among the three substrate materials.