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Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins

Angiogenesis, the process of forming new blood vessels, is crucial in the physiological response to ischemia, though it can be detrimental as part of inflammation and tumorigenesis. We have previously shown that high-density lipoproteins (HDL) modulate angiogenesis in a context-specific manner via d...

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Autores principales: Wong, Nathan K. P., Cheung, Helena, Solly, Emma L., Vanags, Laura Z., Ritchie, William, Nicholls, Stephen J., Ng, Martin K. C., Bursill, Christina A., Tan, Joanne T. M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073236/
https://www.ncbi.nlm.nih.gov/pubmed/29958463
http://dx.doi.org/10.3390/ijms19071903
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author Wong, Nathan K. P.
Cheung, Helena
Solly, Emma L.
Vanags, Laura Z.
Ritchie, William
Nicholls, Stephen J.
Ng, Martin K. C.
Bursill, Christina A.
Tan, Joanne T. M.
author_facet Wong, Nathan K. P.
Cheung, Helena
Solly, Emma L.
Vanags, Laura Z.
Ritchie, William
Nicholls, Stephen J.
Ng, Martin K. C.
Bursill, Christina A.
Tan, Joanne T. M.
author_sort Wong, Nathan K. P.
collection PubMed
description Angiogenesis, the process of forming new blood vessels, is crucial in the physiological response to ischemia, though it can be detrimental as part of inflammation and tumorigenesis. We have previously shown that high-density lipoproteins (HDL) modulate angiogenesis in a context-specific manner via distinct classical signalling pathways, enhancing hypoxia-induced angiogenesis while suppressing inflammatory-driven angiogenesis. Whether additional novel targets exist to account for these effects are unknown. A microarray approach identified two novel genes, cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) and tripartite motif-containing protein 2 (TRIM2) that were upregulated by reconstituted HDL (rHDL). We measured CREBRF and TRIM2 expression in human coronary artery endothelial cells following incubation with rHDL and exposure to either hypoxia or an inflammatory stimulus. We found that CREBRF and TRIM2 mRNA were significantly upregulated by rHDL, particularly in response to its phospholipid component 1-palmitoyl-2-linoleoyl-phosphatidylcholine, however, protein expression was not significantly altered. Knockdown of TRIM2 impaired endothelial cell tubulogenesis in vitro in both hypoxia and inflammation, implying a necessary role in angiogenesis. Furthermore, TRIM2 knockdown attenuated rHDL-induced tubule formation in hypoxia, suggesting that it is important in mediating the pro-angiogenic action of rHDL. Our study has implications for understanding the regulation of angiogenesis in both of these pathophysiological contexts by HDL.
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spelling pubmed-60732362018-08-13 Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins Wong, Nathan K. P. Cheung, Helena Solly, Emma L. Vanags, Laura Z. Ritchie, William Nicholls, Stephen J. Ng, Martin K. C. Bursill, Christina A. Tan, Joanne T. M. Int J Mol Sci Article Angiogenesis, the process of forming new blood vessels, is crucial in the physiological response to ischemia, though it can be detrimental as part of inflammation and tumorigenesis. We have previously shown that high-density lipoproteins (HDL) modulate angiogenesis in a context-specific manner via distinct classical signalling pathways, enhancing hypoxia-induced angiogenesis while suppressing inflammatory-driven angiogenesis. Whether additional novel targets exist to account for these effects are unknown. A microarray approach identified two novel genes, cyclic-adenosine-monophosphate-response-element-binding protein 3 regulatory factor (CREBRF) and tripartite motif-containing protein 2 (TRIM2) that were upregulated by reconstituted HDL (rHDL). We measured CREBRF and TRIM2 expression in human coronary artery endothelial cells following incubation with rHDL and exposure to either hypoxia or an inflammatory stimulus. We found that CREBRF and TRIM2 mRNA were significantly upregulated by rHDL, particularly in response to its phospholipid component 1-palmitoyl-2-linoleoyl-phosphatidylcholine, however, protein expression was not significantly altered. Knockdown of TRIM2 impaired endothelial cell tubulogenesis in vitro in both hypoxia and inflammation, implying a necessary role in angiogenesis. Furthermore, TRIM2 knockdown attenuated rHDL-induced tubule formation in hypoxia, suggesting that it is important in mediating the pro-angiogenic action of rHDL. Our study has implications for understanding the regulation of angiogenesis in both of these pathophysiological contexts by HDL. MDPI 2018-06-28 /pmc/articles/PMC6073236/ /pubmed/29958463 http://dx.doi.org/10.3390/ijms19071903 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wong, Nathan K. P.
Cheung, Helena
Solly, Emma L.
Vanags, Laura Z.
Ritchie, William
Nicholls, Stephen J.
Ng, Martin K. C.
Bursill, Christina A.
Tan, Joanne T. M.
Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title_full Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title_fullStr Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title_full_unstemmed Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title_short Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins
title_sort exploring the roles of crebrf and trim2 in the regulation of angiogenesis by high-density lipoproteins
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073236/
https://www.ncbi.nlm.nih.gov/pubmed/29958463
http://dx.doi.org/10.3390/ijms19071903
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