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

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 potentia...

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Main Authors: 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
Format: Article
Language:English
Published: BMC 2017-03-01
Series:Journal of Hematology & Oncology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13045-017-0440-0
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author 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
author_facet 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
author_sort Hangfei Fu
collection DOAJ
description 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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spelling doaj.art-82acf15a6e2b4277874048672e7520252022-12-21T19:00:41ZengBMCJournal of Hematology & Oncology1756-87222017-03-0110112110.1186/s13045-017-0440-0Thrombus 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 studyHangfei Fu0Nish Vadalia1Eric R. Xue2Candice Johnson3Luqiao Wang4William Y. Yang5Claudette Sanchez6Jun Nelson7Qian Chen8Eric T. Choi9Jian-Xing Ma10Jun Yu11Hong Wang12Xiaofeng Yang13Department of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Physiology, University of Oklahoma College of MedicineDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Physiology, University of Oklahoma College of MedicineDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityDepartment of Pharmacology, Lewis Katz School of Medicine at Temple UniversityAbstract 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.http://link.springer.com/article/10.1186/s13045-017-0440-0Angiogenic genesTissue expression of genesPathological modulation of angiogenesisImmune regulation of angiogenesisAngiogenic leukocytes
spellingShingle 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
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
Journal of Hematology & Oncology
Angiogenic genes
Tissue expression of genes
Pathological modulation of angiogenesis
Immune regulation of angiogenesis
Angiogenic leukocytes
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Angiogenic genes
Tissue expression of genes
Pathological modulation of angiogenesis
Immune regulation of angiogenesis
Angiogenic leukocytes
url http://link.springer.com/article/10.1186/s13045-017-0440-0
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