The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
MicroRNA-24 Regulates Vascularity After Myocardial Infarction
Open accessAbstract
Background—: Myocardial infarction leads to cardiac remodeling and development of heart failure. Insufficient myocardial capillary density after myocardial infarction has been identified as a critical event in this process, although the underlying mechanisms of cardiac angiogenesis are mechanistically not well understood. Methods and Results—: Here, we show that the small noncoding RNA microRNA-24 (miR-24) is enriched in cardiac endothelial cells and considerably upregulated after cardiac ischemia. MiR-24 induces endothelial cell apoptosis, abolishes endothelial capillary network formation on Matrigel, and inhibits cell sprouting from endothelial spheroids. These effects are mediated through targeting of the endothelium-enriched transcription factor GATA2 and the p21-activated kinase PAK4, which were identified by bioinformatic predictions and validated by luciferase gene reporter assays. Respective downstream signaling cascades involving phosphorylated BAD (Bcl-XL/Bcl-2–associated death promoter) and Sirtuin1 were identified by transcriptome, protein arrays, and chromatin immunoprecipitation analyses. Overexpression of miR-24 or silencing of its targets significantly impaired angiogenesis in zebrafish embryos. Blocking of endothelial miR-24 limited myocardial infarct size of mice via prevention of endothelial apoptosis and enhancement of vascularity, which led to preserved cardiac function and survival. Conclusions—: Our findings indicate that miR-24 acts as a critical regulator of endothelial cell apoptosis and angiogenesis and is suitable for therapeutic intervention in the setting of ischemic heart disease.
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Cites
The functions of animal microRNAs
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A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing
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Self-citationMicroRNA-21 contributes to myocardial disease by stimulating MAP kinase signalling in fibroblasts
Thum, T., Gross, C., Fiedler, J., Fischer, T., Kissler, S., Bussen, M., Galuppo, P., Just, S., Rottbauer, W., Frantz, S., et al. (2008) · Nature · doi:10.1038/nature07511 · Cited by 2,349
Self-citationPervasive roles of microRNAs in cardiovascular biology
Small, E. M., & Olson, E. N. (2011) · Nature · doi:10.1038/nature09783 · Cited by 1,180
A MicroRNA Signature of Hypoxia
Kulshreshtha, R., Ferracin, M., Wojcik, S. E., Garzon, R., Alder, H., Agosto-Perez, F. J., Davuluri, R., Liu, C.-G., Croce, C. M., Negrini, M., et al. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.01395-06 · Cited by 1,055
SIRT1 Controls Endothelial Angiogenic Functions During Vascular Growth
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Melkman‐Zehavi, T., Oren, R., Kredo‐Russo, S., Shapira, T., Mandelbaum, A. D., Rivkin, N., Nir, T., Lennox, K. A., Behlke, M. A., Dor, Y., et al. (2011) · The EMBO Journal · doi:10.1038/emboj.2010.361 · Cited by 280
Cited by
MicroRNA therapeutics for cardiovascular disease: opportunities and obstacles
van Rooij, E., & Olson, E. N. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3864 · Cited by 624
PAK signalling during the development and progression of cancer
Radu, M., Semenova, G., Kosoff, R., & Chernoff, J. (2014) · Nature Reviews Cancer · doi:10.1038/nrc3645 · Cited by 503
Animal Models of Heart Failure: A Scientific Statement From the American Heart Association
Houser, S. R., Margulies, K. B., Murphy, A. M., Spinale, F. G., Francis, G. S., Prabhu, S. D., Rockman, H. A., Kass, D. A., Molkentin, J. D., Sussman, M. A., et al. (2012) · Circulation Research · doi:10.1161/res.0b013e3182582523 · Cited by 435
Lekka, E., & Hall, J. (2018) · FEBS Letters · doi:10.1002/1873-3468.13182 · Cited by 251
MicroRNA-26a Regulates Pathological and Physiological Angiogenesis by Targeting BMP/SMAD1 Signaling
Icli, B., Wara, A. K. M., Moslehi, J., Sun, X., Plovie, E., Cahill, M., Marchini, J. F., Schissler, A., Padera, R. F., Shi, J., et al. (2013) · Circulation Research · doi:10.1161/circresaha.113.301780 · Cited by 211
Metadata
- Authors
- Fiedler, J., Jazbutyte, V., Kirchmaier, B. C., Gupta, S. K., Lorenzen, J., Hartmann, D., Galuppo, P., Kneitz, S., Pena, J. T. G., Sohn-Lee, C., Loyer, X., Soutschek, J., Brand, T., Tuschl, T., Heineke, J., Martin, U., Schulte-Merker, S., Ertl, G., Engelhardt, S., Bauersachs, J., & Thum, T.
- Venue
- Circulation
- Published
- 2011-08-09
- Volume
- 124
- Issue
- 6
- Pages
- 720-730
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2137730290
- Cited by
- 393
- References
- 7
- FWCI
- 13.74
- Type
- journal article
- Language
- en
- Open access
- bronze
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- The paper
- Fiedler, J., Jazbutyte, V., Kirchmaier, B. C., Gupta, S. K., Lorenzen, J., Hartmann, D., Galuppo, P., Kneitz, S., Pena, J. T. G., Sohn-Lee, C., Loyer, X., Soutschek, J., Brand, T., Tuschl, T., Heineke, J., Martin, U., Schulte-Merker, S., Ertl, G., Engelhardt, S., . . . Thum, T. (2011). MicroRNA-24 Regulates Vascularity After Myocardial Infarction. Circulation. https://doi.org/10.1161/circulationaha.111.039008
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