| BMC Cardiovascular Disorders | |
| The influence of statins on the free intracellular calcium concentration in human umbilical vein endothelial cells | |
| Stefan H Heinemann1  Hans R Figulla2  Gero Schwarz2  Stephan Heinke2  | |
| [1] Unit Molecular and Cellular Biophysics Med. Faculty of the Friedrich Schiller University Jena Drackendorfer St. 1, D-07747 Jena, Germany;Clinics for Internal Medicine I Med. Faculty of the Friedrich Schiller University Jena Erlanger Allee 101, D-07747 Jena, Germany | |
| 关键词: Arteriosclerosis.; Hydroxymethylglutaryl CoA Reductase Inhibitors; Nitric Oxide; Free Intracelluar Calcium; Endothelium; | |
| Others : 1088605 DOI : 10.1186/1471-2261-4-4 |
|
| received in 2003-10-05, accepted in 2004-05-04, 发布年份 2004 | |
PDF
|
|
【 摘 要 】
Background
Statins are cholesterol-lowering drugs that are widely used to reduce the risk of cardiac infarction. Their beneficial clinical effects, however, are not restricted to their influence on cholesterol production. As several studies have shown that they have a potency of relaxing blood vessels.
Methods
We measured the effects of statins on the intracellular free calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVEC) after acute application and 24-h-preincubation of statins.
Results
Incubation of the cells for 24 h with cerivastatin or fluvastatin significantly increased the resting [Ca2+]i. For cerivastatin this effect manifested at a concentration of 1 μM. Increase of resting [Ca2+]i in the presence of cerivastatin also occurred when the nitric oxide synthase was inhibited. Transient Ca2+ release induced by histamine was not affected.
Conclusions
The increase of resting [Ca2+]i after incubation with cerivastatin or fluvastatin may provide an explanation for the direct effects of statins on the endothelial-dependent vasodilatation and restoration of endothelial activity in vivo.
【 授权许可】
2004 Heinke et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
【 预 览 】
| Files | Size | Format | View |
|---|---|---|---|
| 20150119020920832.pdf | 286KB | ||
| Figure 2. | 23KB | Image | |
| Figure 1. | 30KB | Image |
【 图 表 】
Figure 1.
Figure 2.
【 参考文献 】
- [1]Alvarez de Sotomayor M, Herrera MD, Marhuenda E, Andriantsitohaina R: Characterization of endothelial factors involved in the vasodilatory effect of simvastatin in aorta and small mesenteric artery of the rat. Br J Pharmacol 2000, 131:1179-1187.
- [2]Boer R, Ulrich WR, Klein T, Mirau B, Haas S, Baur I: The inhibitory potency and selectivity of arginine substrate site nitric-oxide synthase inhibitors is solely determined by their affinity toward the different isoenzymes. Mol Pharmacol 2000, 58(5):1026-34.
- [3]Endres M, Laufs U, Huang Z, Nakamura T, Huang P, Moskowitz MA, Liao JK: Stroke protection by 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors mediated by endothelial nitric oxide synthase. Proc Natl Acad Sci USA 1998, 95:8880-8885.
- [4]Fleming I, Busse R: Signal transduction of eNOS activation. Cardiovasc Res 1999, 43:532-541.
- [5]Govers R, Rabelink TJ: Cellular regulation of endothelial nitric oxide synthase. Am J Physiol Renal Physiol 2001, 280:F193-206.
- [6]Grynkiewicz G, Poenie M, Tsien RY: A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 1985, 260:3440-3450.
- [7]Hernandez-Perera O, Perez-Sala D, Navarro-Antolin J, Sanchez-Pascuala R, Hernandez G, Diaz C, Lamas S: Effects of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors, atorvastatin and simvastatin, on the expression of endothelin-1 and endothelial nitric oxide synthase in vascular endothelial cells. J Clin Invest 1998, 101:2711-2719.
- [8]Kaesemeyer WH, Caldwell RB, Huang J, Caldwell RW: Pravastatin sodium activates endothelial nitric oxide synthase independent of its cholesterol-lowering actions. Am Coll Cardiol 1999, 33:234-241.
- [9]Laufs U, la Fata V, Plutzky J, Liao JK: Upregulation of endothelial nitric oxide synthase by HMG CoA reductase inhibitors. Circulation 1998, 97:1129-1135.
- [10]Laufs U, Liao JK: Post-transcriptional regulation of endothelial nitric oxide synthase mRNA stability by Rho GTPase. J Biol Chem 1998, 273:24266-24271.
- [11]Mak DO, McBride S, Foskett JK: Inositol 1,4,5-trisphosphate activation of inositol trisphosphate receptor Ca2+ channel by ligand tuning of Ca2+ inhibition. Proc Natl Acad Sci U S A 1999, 95(26):15821-5.
- [12]Mizuno O, Kobayashi S, Hirano K, Nishimura J, Kubo C, Kanaide H: Stimulus-specific alteration of the relationship between cytosolic Ca2+ transients and nitric oxide production in endothelial cells ex vivo. Br J Pharmacol 2000, 130:1140-1146.
- [13]Muck W: Clinical pharmacokinetics of Cerivastatin. Clin Pharmacokinet 2000, 39:99-116.
- [14]O'Driscoll G, Green D, Taylor RR: Simvastatin, an HMG-coenzyme A reductase inhibitor, improves endothelial function within 1 month. Circulation 1997, 95:1126-1131.
- [15]Sacks FM, Pfeffer MA, Moye LA: The effect of Pravastatin on coronary events after myocardial infarction in patient with average cholesterol levels. N Engl J Med 1996, 335:1001-1009.
- [16]Shepherd J, Cobbe SM, Ford I: Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West Of Scotland Coronary Study Group. N Engl J Med 1995, 333:1301-1307.
- [17]Volk T, Mading K, Hensel M, Kox WJ: Nitric oxide induces transient Ca2+ changes in endothelial cells independent of cGMP. J Cell Physiol 1997, 172:296-305.
- [18]Wagner AH, Kohler T, Ruckschloss U, Just I, Hecker M: Improvement of nitric oxide-dependent vasodilatation by HMG-CoA reductase inhibitors through attenuation of endothelial superoxide anion formation. Arterioscler Thromb Vasc Biol 2000, 20:61-69.
- [19]Yamada M, Huang Z, Dalkara T, Endres M, Laufs U, Waeber C, Huang PL, Liao JK, Moskowitz MA: Endothelial nitric oxide synthase-dependent cerebral blood flow augmentation by L-arginine after chronic statin treatment. J Cereb Blood Flow Metab 2000, 20:709-717.
PDF