The DOI matches its Crossref record; 38 of the 38 references it cites were found in a registry or an index.
Statins Exert Endothelial Atheroprotective Effects via the KLF2 Transcription Factor
Open accessAbstract
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, statins, have been shown to positively impact vascular function independent of their plasma lipid-lowering action. Several of these beneficial effects involve modulation of gene expression. Here we explored whether the transcription factor Kruppel-like factor 2 (KLF2), a biomechanically activated gene we recently identified as part of the endothelial "atheroprotective phenotype," is regulated by statins and whether this mechanism is important for the non-lipid lowering beneficial effects mediated by these drugs in endothelium. The mRNA levels of KLF2 in human umbilical vein endothelial cells increased in the presence of various statins. KLF2 induction was observed within 8 h after drug treatment and remained elevated for at least 24 h. This statin effect on KLF2 expression was reversed by addition of mevalonate and its downstream metabolite geranygeranyl pyrophosphate. Furthermore, inhibition of protein geranylgeranylation with GGTI-298 significantly induced KLF2 levels, whereas inhibition of farnesylation did not. Statin-mediated KLF2 expression was followed by the up-regulation of several of its downstream transcriptional targets. Using small interfering RNA to block KLF2 expression, we demonstrated that this transcription factor is necessary for the statin-mediated regulation of several pathophysiologically relevant genes. These results strongly implicate KLF2 as a transcriptional regulator of the statin-mediated effects in vascular endothelium and provide a novel mechanism for the well established non-lipid lowering beneficial cardiovascular effects of statins.
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C-Reactive Protein Levels and Outcomes after Statin Therapy
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PLEIOTROPIC EFFECTS OF STATINS
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Upregulation of Endothelial Nitric Oxide Synthase by HMG CoA Reductase Inhibitors
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KLF2 Is a Novel Transcriptional Regulator of Endothelial Proinflammatory Activation
SenBanerjee, S., Lin, Z., Atkins, G. B., Greif, D. M., Rao, R. M., Kumar, A., Feinberg, M. W., Chen, Z., Simon, D. I., Luscinskas, F. W., et al. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20031132 · Cited by 723
Self-citation
Cited by
Mammalian Krüppel-Like Factors in Health and Diseases
McConnell, B. B., & Yang, V. W. (2010) · Physiological Reviews · doi:10.1152/physrev.00058.2009 · Cited by 1,018
Anti-Inflammatory Effects of Statins: Clinical Evidence and Basic Mechanisms
Jain, M. K., & Ridker, P. M. (2005) · Nature Reviews Drug Discovery · doi:10.1038/nrd1901 · Cited by 915
Demierre, M.-F., Higgins, P. D. R., Gruber, S. B., Hawk, E., & Lippman, S. M. (2005) · Nature Reviews Cancer · doi:10.1038/nrc1751 · Cited by 819
Vascular endothelium, hemodynamics, and the pathobiology of atherosclerosis
Gimbrone, M. A., & García-Cardeña, G. (2013) · Cardiovascular Pathology · doi:10.1016/j.carpath.2012.06.006 · Cited by 434
Self-citationRole of Krüppel-Like Transcription Factors in Endothelial Biology
Atkins, G. B., & Jain, M. K. (2007) · Circulation Research · doi:10.1161/01.res.0000267856.00713.0a · Cited by 419
Metadata
- Authors
- Parmar, K. M., Nambudiri, V., Dai, G., Larman, H. B., Gimbrone, M. A., & García-Cardeña, G.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2005-07
- Volume
- 280
- Issue
- 29
- Pages
- 26714-26719
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2005517764
- Cited by
- 253
- References
- 38
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- hybrid
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