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Article

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

by
Nathan K. P. Wong
1,2,3,
Helena Cheung
1,2,
Emma L. Solly
3,
Laura Z. Vanags
1,2,
William Ritchie
2,4,5,
Stephen J. Nicholls
3,6,
Martin K. C. Ng
2,7,
Christina A. Bursill
1,2,3,6,† and
Joanne T. M. Tan
1,2,3,6,*,†
1
Immunobiology Research Group, Heart Research Institute, 7 Eliza Street, Newtown, NSW 2042, Australia
2
Discipline of Medicine, The University of Sydney School of Medicine, Camperdown, NSW 2006, Australia
3
Heart Health Theme, South Australian Health and Medical Research Institute, North Terrace, Adelaide, SA 5000, Australia
4
Centenary Institute, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
5
Institute of Human Genetics–CNRS, 141 rue de la Cardonille, 34396 Montpellier CEDEX 5, France
6
Adelaide Medical School, Faculty of Health & Medical Sciences, University of Adelaide, Adelaide, SA 5000, Australia
7
Department of Cardiology, Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
*
Author to whom correspondence should be addressed.
†
Equal author contributions to publication.
Int. J. Mol. Sci. 2018, 19(7), 1903; https://doi.org/10.3390/ijms19071903
Submission received: 8 May 2018 / Revised: 25 June 2018 / Accepted: 26 June 2018 / Published: 28 June 2018
(This article belongs to the Special Issue Cholesterol and Lipoprotein Metabolism)
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Abstract

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.
Keywords: angiogenesis; high-density lipoproteins; hypoxia; inflammation; TRIM2; CREBRF angiogenesis; high-density lipoproteins; hypoxia; inflammation; TRIM2; CREBRF
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MDPI and ACS Style

Wong, N.K.P.; Cheung, H.; Solly, E.L.; Vanags, L.Z.; Ritchie, W.; Nicholls, S.J.; Ng, M.K.C.; Bursill, C.A.; Tan, J.T.M. Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins. Int. J. Mol. Sci. 2018, 19, 1903. https://doi.org/10.3390/ijms19071903

AMA Style

Wong NKP, Cheung H, Solly EL, Vanags LZ, Ritchie W, Nicholls SJ, Ng MKC, Bursill CA, Tan JTM. Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins. International Journal of Molecular Sciences. 2018; 19(7):1903. https://doi.org/10.3390/ijms19071903

Chicago/Turabian Style

Wong, Nathan K. P., Helena Cheung, Emma L. Solly, Laura Z. Vanags, William Ritchie, Stephen J. Nicholls, Martin K. C. Ng, Christina A. Bursill, and Joanne T. M. Tan. 2018. "Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins" International Journal of Molecular Sciences 19, no. 7: 1903. https://doi.org/10.3390/ijms19071903

APA Style

Wong, N. K. P., Cheung, H., Solly, E. L., Vanags, L. Z., Ritchie, W., Nicholls, S. J., Ng, M. K. C., Bursill, C. A., & Tan, J. T. M. (2018). Exploring the Roles of CREBRF and TRIM2 in the Regulation of Angiogenesis by High-Density Lipoproteins. International Journal of Molecular Sciences, 19(7), 1903. https://doi.org/10.3390/ijms19071903

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