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.
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.
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DOI：
10.1186/s13045-017-0440-0
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发表时间：
2017-03-23
影响因子：
28.5
通讯作者：
Yang X
中科院分区：
文献类型：
--
作者：
Fu H;Vadalia N;Xue ER;Johnson C;Wang L;Yang WY;Sanchez C;Nelson J;Chen Q;Choi ET;Ma JX;Yu J;Wang H;Yang X
目前针对癌症和心血管疾病的血管生成疗法尚未达到预期的效果，这反映了对血管生成的进一步了解的必要性。在本研究中，我们重点解决了组织在生理状态下是否具有不同的血管生成电位（angiogenic potential, APs），以及在各种疾病状态下血管生成是如何被调节的问题。在健康和患病的人和小鼠组织中，我们分析了163个血管生成基因的表达，包括转录调节因子（TRs）、生长因子和受体（GF/Rs）、细胞因子和趋化因子（C/Cs）、蛋白酶和抑制剂（P/Is）。TRs分为炎性、稳态和内皮细胞特异性TRs， C/C分为促血管生成、抗血管生成和双功能C/C。结果表明：(1)人体的心脏、肌肉、眼睛、胰腺和淋巴结是APs最高的组织；(2)高APs的组织有更活跃的血管生成途径和血管生成C/C反应；(3)炎性TRs主导所有血管生成C/Cs的调控；而内皮细胞特异性TRs主要调控促血管生成和双功能C/C；(4)组织AP与氧传感器PHD2、HIF1B、VEGF通路基因VEGFB、干细胞基因SOX2的表达呈正相关；(5)消化系统肿瘤血管生成以内皮细胞特异性促血管生成途径为主，而肺癌和前列腺癌血管生成明显减少；(6)急性冠状动脉疾病患者血栓源性白细胞中内皮细胞特异性促血管生成途径显著增加。我们的研究结果表明，血栓来源的白细胞表达更多内皮细胞特异性血管生成标志物，直接促进心肌梗死后的血管生成，某些实体肿瘤可能比其他实体肿瘤对抗血管生成治疗更敏感。本文的在线版本（doi:10.1186/s13045-017-0440-0）包含补充材料，仅供授权用户使用。
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. The online version of this article (doi:10.1186/s13045-017-0440-0) contains supplementary material, which is available to authorized users.