Atherosclerosis
Volume 208, Issue 1 , Pages 50-55 , January 2010

Lovastatin inhibits oxidized L-A-phosphatidylcholine B-arachidonoyl-gamma-palmitoyl (ox-PAPC)-stimulated interleukin-8 mRNA and protein synthesis in human aortic endothelial cells by depleting stores of geranylgeranyl pyrophosphate

  • Lucas A. Dvoracek

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Jeffrey I. Kreisberg

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Jordan McKinney

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Gabrielle Schmid

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Amanda D. Francis

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Katie L. Kacmarik

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Huey Miin Lee

      Affiliations

    • Department of Statistics, West Virginia University, Morgantown, WV 26506-6330, United States
    • ,
  • Melinda S. Detrick

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • ,
  • Donald A. Primerano

      Affiliations

    • Department of Biochemistry and Microbiology, Marshall University, Huntington, WV 25755, United States
    • ,
  • Nalini Santanam

      Affiliations

    • Department of Pharmacology, Physiology & Toxicology, Marshall University, Huntington, WV 25755, United States
    • ,
  • Robert Kreisberg

      Affiliations

    • Department of Natural Sciences and Mathematics, West Liberty University, West Liberty, WV 26074, United States
    • Corresponding Author InformationCorresponding author at: Department of Natural Sciences and Mathematics, West Liberty University, PO Box 295/route 88N, 139 Campus Service Center, West Liberty, WV 26074, United States. Tel.: +1 304 336 8052; fax: +1 304 336 8266.

Received 2 April 2009 ,Revised 11 May 2009 ,Accepted 8 June 2009.

References 

  1. Libby P. Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr. 2006;83:456S–460S
  2. Watson AD, Subbanagounder G, Welsbie DS, et al. Structural identification of a novel pro-inflammatory epoxyisoprostane phospholipid in mildly oxidized low density lipoprotein. J Biol Chem. 1999;274:24787–24798
  3. Kibayashi E, Urakaze M, Kobashi C, et al. Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells. Clin Sci (Lond). 2005;108:515–521
  4. Walton KA, Hsieh X, Gharavi N, et al. Receptors involved in the oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine-mediated synthesis of interleukin-8. A role for Toll-like receptor 4 and a glycosylphosphatidylinositol-anchored protein. J Biol Chem. 2003;278:29661–29666
  5. Reddy S, Hama S, Grijalva V, et al. Mitogen-activated protein kinase phosphatase 1 activity is necessary for oxidized phospholipids to induce monocyte chemotactic activity in human aortic endothelial cells. J Biol Chem. 2001;276:17030–17035
  6. Yeh M, Gharavi NM, Choi J, et al. Oxidized phospholipids increase interleukin 8 (IL-8) synthesis by activation of the c-src/signal transducers and activators of transcription (STAT)3 pathway. J Biol Chem. 2004;279:30175–30181
  7. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195–2207
  8. Ghosh PM, Ghosh-Choudhury N, Moyer ML, et al. Role of RhoA activation in the growth and morphology of a murine prostate tumor cell line. Oncogene. 1999;18:4120–4130
  9. Lefer AM, Scalia R, Lefer DJ. Vascular effects of HMG CoA-reductase inhibitors (statins) unrelated to cholesterol lowering: new concepts for cardiovascular disease. Cardiovasc Res. 2001;49:281–287
  10. Li X, Liu L, Tupper JC, et al. Inhibition of protein geranylgeranylation and RhoA/RhoA kinase pathway induces apoptosis in human endothelial cells. J Biol Chem. 2002;277:15309–15316
  11. Grunler J, Ericsson J, Dallner G. Branch-point reactions in the biosynthesis of cholesterol, dolichol, ubiquinone and prenylated proteins. Biochim Biophys Acta. 1994;1212:259–277
  12. Sinensky M, Lutz RJ. The prenylation of proteins. BioEssays. 1992;14:25–31
  13. Bourne HR, Sanders DA, McCormick F. The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 1990;348:125–132
  14. Bochkov VN, Mechtcheriakova D, Lucerna M, et al. Oxidized phospholipids stimulate tissue factor expression in human endothelial cells via activation of ERK/EGR-1 and Ca(++)/NFAT. Blood. 2002;99:199–206
  15. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001;25:402–408
  16. Hall A. Rho GTPases and the actin cytoskeleton. Science. 1998;279:509–514
  17. Takai Y, Sasaki T, Tanaka K, Nakanishi H. Rho as a regulator of the cytoskeleton. Trends Biochem Sci. 1995;20:227–231
  18. Ghosh PM, Mott GE, Ghosh-Choudhury N, et al. Lovastatin induces apoptosis by inhibiting mitotic and post-mitotic events in cultured mesangial cells. Biochim Biophys Acta. 1997;1359:13–24
  19. Chrzanowska-Wodnicka M, Burridge K. Rho-stimulated contractility drives the formation of stress fibers and focal adhesions. J Cell Biol. 1996;133:1403–1415
  20. Kreisberg JI, Ghosh-Choudhury N, Radnik RA, Schwartz MA. Role of Rho and myosin phosphorylation in actin stress fiber assembly in mesangial cells. Am J Physiol. 1997;273:F283–288
  21. Bragina EE, Vasiliev JM, Gelfand IM. Formation of bundles of microfilaments during spreading of fibroblasts on the substrate. Exp Cell Res. 1976;97:241–248
  22. Nobes CD, Hall A. Rho, rac, and cdc42 GTPases regulate the assembly of multimolecular focal complexes associated with actin stress fibers, lamellipodia, and filopodia. Cell. 1995;81:53–62
  23. Wong B, Lumma WC, Smith AM, et al. Statins suppress THP-1 cell migration and secretion of matrix metalloproteinase 9 by inhibiting geranylgeranylation. J Leukoc Biol. 2001;69:959–962
  24. Essler M, Retzer M, Bauer M, et al. Stimulation of platelets and endothelial cells by mildly oxidized LDL proceeds through activation of lysophosphatidic acid receptors and the Rho/Rho-kinase pathway. Inhibition by lovastatin. Ann N Y Acad Sci. 2000;905:282–286
  25. Wojciak-Stothard B, Williams L, Ridley AJ. Monocyte adhesion and spreading on human endothelial cells is dependent on Rho-regulated receptor clustering. J Cell Biol. 1999;145:1293–1307
  26. Ridker PM, Danielson E, Fonseca FA, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet. 2009;

PII: S0021-9150(09)00488-2

doi: 10.1016/j.atherosclerosis.2009.06.013

Atherosclerosis
Volume 208, Issue 1 , Pages 50-55 , January 2010

Article Tools

* Image Usage & Resolution