The online version of this article (doi:10.1186/s13045-017-0440-0) contains supplementary material, which is available to authorized users.
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.
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.
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.
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.
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
Du F, Zhou J, Gong R, Huang X, Pansuria M, Virtue A, et al. Endothelial progenitor cells in atherosclerosis. Front Biosci (Landmark Ed). 2012;17:2327–49. CrossRef
Wang L, Fu H, Nanayakkara G, Li Y, Shao Y, Johnson C, et al. Novel extracellular and nuclear caspase-1 and inflammasomes propagate inflammation and regulate gene expression: a comprehensive database mining study. J Hematol & Oncol. 2016;9:122. CrossRef
Yin Y, Li X, Sha X, Xi H, Li YF, Shao Y, et al. Early hyperlipidemia promotes endothelial activation via a caspase-1-sirtuin 1 pathway. Arter Thromb Vasc Biol. 2015;35:804–16. CrossRef
Li Y-F, Huang X, Li X, Gong R, Yin Y, Nelson J, et al. Caspase-1 mediates hyperlipidemia-weakened progenitor cell vessel repair. Front Biosci (Landmark Ed). 2016;21:178–91. CrossRef
Yang WY, Shao Y, Lopez-Pastrana J, Mai J, Wang H, Yang X. Pathological conditions re-shape physiological Tregs into pathological Tregs. Burn Trauma. 2015;3:1. CrossRef
National Center of Biotechnology Information Unigene Library. http://www.ncbi.nlm.nih.gov/unigene. Accessed March 2016.
NCBI GEO2R. http://www.ncbi.nlm.nih.gov/geo/geo2r/. Accessed May 2016.
Ingenuity Pathway Analysis. http://www.ingenuity.com/. Accessed October 2016.
Genecards. http://www.genecards.org/. Accessed December 2016.
Binder JX, Pletscher-Frankild S, Tsafou K, Stolte C, O’Donoghue SI, Schneider R, et al. COMPARTMENTS: unification and visualization of protein subcellular localization evidence. Database. 2014;2014:bau012-bau012.
Jeltsch M, Leppänen VM, Saharinen P, Alitalo K. Receptor tyrosine kinase-mediated angiogenesis. Cold Spring Harb Perspect Biol. 2013;5.
Jakob P, Kacprowski T, Briand-Schumacher S, Heg D, Klingenberg R, Stähli BE, et al. Profiling and validation of circulating microRNAs for cardiovascular events in patients presenting with ST-segment elevation myocardial infarction. Eur Heart J. 2016:ehw563.
Tian H, Mcknight SL, Russell DW. Endothelial PAS domain protein 1 (EPAS1), a transcription factor selectively expressed in endothelial cells. 1997:72–82.
Schefter T, Jackson M, Rusthoven C, Fisher C. Clinical potential of bevacizumab in the treatment of metastatic and locally advanced cervical cancer: current evidence. Oncol Targets Ther. 2014;7:751. CrossRef
Ranpura V, Hapani S, Chuang J, Wu S. Risk of cardiac ischemia and arterial thromboembolic events with the angiogenesis inhibitor bevacizumab in cancer patients: a meta-analysis of randomized controlled trials. Acta Oncol (Madr). 2010;49:287–97. CrossRef
Tabas I. 2016 Russell Ross Memorial Lecture in Vascular Biology. Arterioscler Thromb Vasc Biol. 2016;:ATVBAHA.116.308036.
- 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
Eric R. Xue
William Y. Yang
Eric T. Choi
- BioMed Central
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