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Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells.
J Physiol Pharmacol 2007; 58(3):503-14JP

Abstract

Endothelial dysfunction and atherosclerosis are associated with an inflammation-induced decrease in endothelial nitric oxide synthase (eNOS) expression. Based on the differences between hydrophobic and hydrophilic statins in their reduction of cardiac events, we analyzed the effects of rosuvastatin and cerivastatin on eNOS and inducible NO synthase (iNOS) expression and NOS activity in TNF-alpha-stimulated human umbilical vein endothelial cells (HUVEC). Both statins reversed down-regulation of eNOS mRNA and protein expression by inhibiting HMG-CoA reductase and isoprenoid synthesis. Cerivastatin tended to a more pronounced effect on eNOS expression compared to rosuvastatin. NOS activity - measured by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline - was enhanced under treatment with both drugs due to inhibition of HMG-CoA reductase. Statin-treatment reduced iNOS mRNA expression under normal conditions, but had no relevant effects on iNOS mRNA expression in cytokine-treated cells. Rosuvastatin and cerivastatin reverse the detrimental effects of TNF-alpha-induced down-regulation in eNOS protein expression and increase NO synthase activity by inhibiting HMG-CoA reductase and subsequent blocking of isoprenoid synthesis. These results provide evidence that statins have beneficial effects by increasing eNOS expression and activity during the atherosclerotic process.

Authors+Show Affiliations

Department of Internal Medicine B, Ernst Moritz Arndt University, Greifswald, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17928646

Citation

Jantzen, F, et al. "Isoprenoid Depletion By Statins Antagonizes Cytokine-induced Down-regulation of Endothelial Nitric Oxide Expression and Increases NO Synthase Activity in Human Umbilical Vein Endothelial Cells." Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, vol. 58, no. 3, 2007, pp. 503-14.
Jantzen F, Könemann S, Wolff B, et al. Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells. J Physiol Pharmacol. 2007;58(3):503-14.
Jantzen, F., Könemann, S., Wolff, B., Barth, S., Staudt, A., Kroemer, H. K., ... Landsberger, M. (2007). Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells. Journal of Physiology and Pharmacology : an Official Journal of the Polish Physiological Society, 58(3), pp. 503-14.
Jantzen F, et al. Isoprenoid Depletion By Statins Antagonizes Cytokine-induced Down-regulation of Endothelial Nitric Oxide Expression and Increases NO Synthase Activity in Human Umbilical Vein Endothelial Cells. J Physiol Pharmacol. 2007;58(3):503-14. PubMed PMID: 17928646.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Isoprenoid depletion by statins antagonizes cytokine-induced down-regulation of endothelial nitric oxide expression and increases NO synthase activity in human umbilical vein endothelial cells. AU - Jantzen,F, AU - Könemann,S, AU - Wolff,B, AU - Barth,S, AU - Staudt,A, AU - Kroemer,H-K, AU - Dahm,J B, AU - Felix,S B, AU - Landsberger,M, PY - 2007/06/13/received PY - 2007/07/13/accepted PY - 2007/10/12/pubmed PY - 2007/12/22/medline PY - 2007/10/12/entrez SP - 503 EP - 14 JF - Journal of physiology and pharmacology : an official journal of the Polish Physiological Society JO - J. Physiol. Pharmacol. VL - 58 IS - 3 N2 - Endothelial dysfunction and atherosclerosis are associated with an inflammation-induced decrease in endothelial nitric oxide synthase (eNOS) expression. Based on the differences between hydrophobic and hydrophilic statins in their reduction of cardiac events, we analyzed the effects of rosuvastatin and cerivastatin on eNOS and inducible NO synthase (iNOS) expression and NOS activity in TNF-alpha-stimulated human umbilical vein endothelial cells (HUVEC). Both statins reversed down-regulation of eNOS mRNA and protein expression by inhibiting HMG-CoA reductase and isoprenoid synthesis. Cerivastatin tended to a more pronounced effect on eNOS expression compared to rosuvastatin. NOS activity - measured by conversion of [(3)H]-L-arginine to [(3)H]-L-citrulline - was enhanced under treatment with both drugs due to inhibition of HMG-CoA reductase. Statin-treatment reduced iNOS mRNA expression under normal conditions, but had no relevant effects on iNOS mRNA expression in cytokine-treated cells. Rosuvastatin and cerivastatin reverse the detrimental effects of TNF-alpha-induced down-regulation in eNOS protein expression and increase NO synthase activity by inhibiting HMG-CoA reductase and subsequent blocking of isoprenoid synthesis. These results provide evidence that statins have beneficial effects by increasing eNOS expression and activity during the atherosclerotic process. SN - 0867-5910 UR - https://www.unboundmedicine.com/medline/citation/17928646/Isoprenoid_depletion_by_statins_antagonizes_cytokine_induced_down_regulation_of_endothelial_nitric_oxide_expression_and_increases_NO_synthase_activity_in_human_umbilical_vein_endothelial_cells_ L2 - http://www.jpp.krakow.pl/journal/archive/09_07/pdf/503_09_07_article.pdf DB - PRIME DP - Unbound Medicine ER -