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01.12.2017 | Research | Ausgabe 1/2017 Open Access

Journal of Hematology & Oncology 1/2017

Thrombus leukocytes exhibit more endothelial cell-specific angiogenic markers than peripheral blood leukocytes do in acute coronary syndrome patients, suggesting a possibility of trans-differentiation: a comprehensive database mining study

Zeitschrift:
Journal of Hematology & Oncology > Ausgabe 1/2017
Autoren:
Hangfei Fu, Nish Vadalia, Eric R. Xue, Candice Johnson, Luqiao Wang, William Y. Yang, Claudette Sanchez, Jun Nelson, Qian Chen, Eric T. Choi, Jian-Xing Ma, Jun Yu, Hong Wang, Xiaofeng Yang
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​s13045-017-0440-0) contains supplementary material, which is available to authorized users.

Abstract

Background

Current angiogenic therapies for cancers and cardiovascular diseases have not yet achieved expected benefits, which reflects the need for improved understanding of angiogenesis. In this study, we focused on solving the problem of whether tissues have different angiogenic potentials (APs) in physiological conditions and how angiogenesis is regulated in various disease conditions.

Methods

In healthy and diseased human and mouse tissues, we profiled the expression of 163 angiogenic genes, including transcription regulators (TRs), growth factors and receptors (GF/Rs), cytokines and chemokines (C/Cs), and proteases and inhibitors (P/Is). TRs were categorized as inflammatory, homeostatic, and endothelial cell-specific TRs, and C/Cs were categorized as pro-angiogenic, anti-angiogenic, and bi-functional C/Cs.

Results

We made the following findings: (1) the human heart, muscle, eye, pancreas, and lymph node are among the tissues with the highest APs; (2) tissues with high APs have more active angiogenic pathways and angiogenic C/C responses; (3) inflammatory TRs dominate regulation of all angiogenic C/Cs; homeostatic TRs regulate all to a lower extent, while endothelial cell-specific TRs mainly regulate pro-angiogenic and bi-functional C/Cs; (4) tissue AP is positively correlated with the expression of oxygen sensors PHD2 and HIF1B, VEGF pathway gene VEGFB, and stem cell gene SOX2; (5) cancers of the digestive system tend to have increased angiogenesis dominated by endothelial cell-specific pro-angiogenic pathways, while lung cancer and prostate cancer have significantly decreased angiogenesis; and (6) endothelial cell-specific pro-angiogenic pathways are significantly increased in thrombus-derived leukocytes in patients with acute coronary artery disease.

Conclusions

Our results demonstrate that thrombus-derived leukocytes express more endothelial cell-specific angiogenic markers to directly promote angiogenesis after myocardial infarction and that certain solid tumors may be more sensitive to anti-angiogenic therapies than others.

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Zusatzmaterial
Additional file 1: Figure S1. Correlation of mRNA relative expression levels of specific genes with angiogenic potential in human tissues. Simple linear regression was applied to the mRNA relative expression levels (Y-axis) against angiogenic potentials (X-axis) in each group of angiogenic genes (transcription regulators, growth factors and receptors, cytokines and chemokines, and proteases, inhibitors, and others). Table S1. Summary of 163 genes related to angiogenesis.
13045_2017_440_MOESM1_ESM.docx
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