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.

Publisher: Biomed Central Country of Publication: England NLM ID: 101468937 Publication Model: Electronic Cited Medium: Internet ISSN: 1756-8722 (Electronic) Linking ISSN: 17568722 NLM ISO Abbreviation: J Hematol Oncol Subsets: MEDLINE

Original Publication: [London] : Biomed Central, 2008-

Cell Transdifferentiation* ; Endothelial Cells* ; Neovascularization, Physiologic*; Acute Coronary Syndrome/*physiopathology ; Leukocytes/*pathology ; Thrombosis/*pathology; Angiogenic Proteins/genetics ; Animals ; Biomarkers ; Data Mining ; Humans ; Mice ; Myocardial Infarction/physiopathology ; Neoplasms/blood supply ; Neoplasms/physiopathology ; Neovascularization, Pathologic/physiopathology ; Transcriptome

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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R01 HL138749 United States HL NHLBI NIH HHS; R01 HL126933 United States HL NHLBI NIH HHS; R01 DK113775 United States DK NIDDK NIH HHS; R01 HL117654 United States HL NHLBI NIH HHS; R01 HL130233 United States HL NHLBI NIH HHS; R01 DK104116 United States DK NIDDK NIH HHS; R01 HL132399 United States HL NHLBI NIH HHS

Keywords: Angiogenic genes; Angiogenic leukocytes; Immune regulation of angiogenesis; Pathological modulation of angiogenesis; Tissue expression of genes

0 (Angiogenic Proteins)
0 (Biomarkers)

Date Created: 20170325 Date Completed: 20171128 Latest Revision: 20220223

20221213

PMC5364721

10.1186/s13045-017-0440-0

28335793