Nucleolin mediated pro-angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post-transcriptional regulation of VEGF-A and MMP-9.
Nucleolin mediated pro-angiogenic role of Hydroxysafflor Yellow A in ischaemic cardiac dysfunction: Post-transcriptional regulation of VEGF-A and MMP-9.
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DOI：
10.1111/jcmm.13552
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发表时间：
2018-05
影响因子：
5.3
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Zou J;Wang N;Liu M;Bai Y;Wang H;Liu K;Zhang H;Xiao X;Wang K
羟基红花黄色素A（HSYA）是红花的最具代表性成分，在中国长期用于治疗缺血性心血管疾病，并表现出显著的抗凝和促血管生成活性，但其潜在机制在很大程度上仍不清楚。本研究旨在进一步阐明HSYA对缺血性心功能不全的促血管生成作用及其机制。建立C57小鼠急性心肌梗死（AMI）模型，术后立即腹腔注射HSYA 25 mg/kg，早晚各1次，连续2周。研究发现，HSYA可明显改善缺血性心脏血流动力学，提高存活率，减轻心肌损伤，并增加缺血心肌中CD 31、血管内皮生长因子-A（VEGF-A）和核仁素的表达。此外，HSYA还能促进人脐静脉内皮细胞（HUVECs）的迁移和管腔形成，增强核仁素、VEGF-A和基质金属蛋白酶-9（MMP-9）的表达，并呈剂量和时间依赖性。然而，核仁素表达的下调显著消除了HSYA的上述作用。进一步的蛋白-RNA免疫共沉淀和免疫沉淀-RT-PCR检测显示核仁素与VEGF-A和MMP-9 mRNA结合，核仁素过表达通过增强VEGF-A和MMP-9 mRNA的稳定性上调VEGF-A和MMP-9 mRNA的表达。此外，HSYA增加了AMI小鼠心脏抗核蛋白抗体沉淀蛋白提取物中VEGF-A和MMP-9的mRNA表达。我们的数据显示，核仁素通过转录后调节VEGF-A和MMP-9的表达介导了HSYA的促血管生成作用，这有助于HSYA对缺血性心功能不全的保护作用。
Hydroxysafflor Yellow A (HSYA), a most representative ingredient of Carthamus tinctorius L., had long been used in treating ischaemic cardiovascular diseases in China and exhibited prominently anticoagulant and pro‐angiogenic activities, but the underlying mechanisms remained largely unknown. This study aimed to further elucidate the pro‐angiogenic effect and mechanism of HSYA on ischaemic cardiac dysfunction. A C57 mouse model of acute myocardial infarction (AMI) was firstly established, and 25 mg/kg HSYA was intraperitoneally injected immediately after operation and given once, respectively, each morning and evening for 2 weeks. It was found that HSYA significantly improved ischaemia‐induced cardiac haemodynamics, enhanced the survival rate, alleviated the myocardial injury and increased the expressions of CD31, vascular endothelial growth factor‐A (VEGF‐A) and nucleolin in the ischaemic myocardium. In addition, HSYA promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs), enhanced the expressions of nucleolin, VEGF‐A and matrix metalloproteinase‐9 (MMP‐9) in a dose‐ and time‐dependent manner. However, down‐regulation of nucleolin expression sharply abrogated the effect mentioned above of HSYA. Further protein‐RNA coimmunoprecipitation and immunoprecipitation‐RT‐PCR assay showed that nucleolin binded to VEGF‐A and MMP‐9 mRNA and overexpression of nucleolin up‐regulated the mRNA expressions of VEGF‐A and MMP‐9 in the HUVECs through enhancing the stability of VEGF‐A and MMP‐9 mRNA. Furthermore, HSYA increased the mRNA expressions of VEGF‐A and MMP‐9 in the extract of antinucleolin antibody‐precipitated protein from the heart of AMI mice. Our data revealed that nucleolin mediated the pro‐angiogenic effect of HSYA through post‐transcriptional regulation of VEGF‐A and MMP‐9 expression, which contributed to the protective effect of HSYA on ischaemic cardiac dysfunction.
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影响因子：
13.3
作者：
Healy, DL;Rogers, PAW;Wingfield, M
通讯作者：
Wingfield, M
DOI：
10.1016/j.bbrc.2013.12.020
发表时间：
2014-01-10
影响因子：
3.1
作者：
Cheng, Dong-dong;Zhao, Hai-guang;Yang, Qing-cheng
通讯作者：
Yang, Qing-cheng
DOI：
10.1084/jem.20132130
发表时间：
2014-09-22
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Morrison AR;Yarovinsky TO;Young BD;Moraes F;Ross TD;Ceneri N;Zhang J;Zhuang ZW;Sinusas AJ;Pardi R;Schwartz MA;Simons M;Bender JR
通讯作者：
Bender JR
影响因子：
14.9
作者：
Abdelmohsen K;Tominaga K;Lee EK;Srikantan S;Kang MJ;Kim MM;Selimyan R;Martindale JL;Yang X;Carrier F;Zhan M;Becker KG;Gorospe M
通讯作者：
Gorospe M
影响因子：
37.8
作者：
Kornowski, R;Fuchs, S;Epstein, SE
通讯作者：
Epstein, SE