Study on the pathological mechanisms of heart failure by integrative analysis of transcriptomics and proteomics
文献类型：期刊论文
| 作者 | Zhang, Jian2; Wang, Yong2; Wang, Wei2; Wang, Yong3; Lin, Weili1; Zhu, Ruixin4; , |
| 刊名 | JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY
 |
| 出版日期 | 2017 |
| 卷号 | 70期号:16页码:C62-C62 |
| 关键词 | angiogenesis delta-like ligand 4/Notch signaling endothelial cell E-prostanoid receptor subtype 3 tip cell |
| ISSN号 | 0735-1097 |
| DOI | 10.1016/j.jacc.2017.07.212 |
| 文献子类 | Meeting Abstract |
| 英文摘要 | Objective-Angiogenesis is a hallmark of embryonic development and various ischemic and inflammatory diseases. Prostaglandin E2 receptor subtype 3 (EP3) plays an important role in pathophysiologic angiogenesis; however, the precise mechanisms remain unknown. Here, we investigated the role of EP3 in zebra fish embryo and mouse retina angiogenesis and evaluated the underlying mechanisms. Approach and Results-The EP3 receptor was highly expressed in the vasculature in both zebra fish embryos and murine fetal retinas. Pharmacological inhibition or genetic deletion of EP3 significantly reduced vasculature formation in zebra fish embryos and mouse retinas. Further characterization revealed reduced filopodia extension of tip cells in embryonic retinas in EP3-deficient mice. EP3 deletion activated Notch activity by upregulation of delta-like ligand 4 expression in endothelial cells (ECs). Inhibition of Notch signaling rescued the angiogenic defects in EP3-deficient mouse retinas. Moreover, EP3 deficiency led to a significant increase in beta-catenin phosphorylation at Ser675 and nuclear accumulation of beta-catenin in ECs. Knockdown or inhibition of beta-catenin restored the impaired sprouting angiogenesis resulting from EP3 deficiency in ECs. The EP3 receptor depressed protein kinase A activity in ECs by coupling to G alpha i. Inhibition of protein kinase A activity significantly reduced Ser675 phosphorylation and nuclear translocation of beta-catenin, abolished the increased delta-like ligand 4 expression, and subsequently restored the impaired angiogenic capacity of EP3-deficient ECs both in vitro and in vivo. Conclusions-Activation of the EP3 receptor facilitates sprouting angiogenesis through protein kinase A-dependent Notch signaling, suggesting that EP3 and its downstream pathways maybe potential therapeutic targets in the treatment of ischemic diseases. |
| 学科主题 | Cardiovascular System & Cardiology |
| 语种 | 英语 |
| WOS记录号 | WOS:000412550800208 |
| 出版者 | ELSEVIER SCIENCE INC |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/1100]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所 |
| 作者单位 | 1.Chinese Acad Sci Shanghai, CAS MPG Partner Inst Computat Biol, Shanghai Inst Biol Sci, Key Lab Computat Biol, Shanghai, Peoples R China; 2.Beijing Univ Chinese Med, Basic Med Coll, Beijing, Peoples R China; 3.Beijing Univ Chinese Med, Sch Life Sci, Beijing, Peoples R China; 4.Tongji Univ, Sch Life Sci & Technol, Dept Bioinformat, Shanghai, Peoples R China, |
| 推荐引用方式 GB/T 7714 | Zhang, Jian,Wang, Yong,Wang, Wei,et al. Study on the pathological mechanisms of heart failure by integrative analysis of transcriptomics and proteomics[J]. JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY,2017,70(16):C62-C62. |
| APA | Zhang, Jian.,Wang, Yong.,Wang, Wei.,Wang, Yong.,Lin, Weili.,...&,.(2017).Study on the pathological mechanisms of heart failure by integrative analysis of transcriptomics and proteomics.JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY,70(16),C62-C62. |
| MLA | Zhang, Jian,et al."Study on the pathological mechanisms of heart failure by integrative analysis of transcriptomics and proteomics".JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY 70.16(2017):C62-C62. |
入库方式： OAI收割
来源：上海营养与健康研究所
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