Abstract
3-Hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to block leukocyte-endothelial interaction independently of their cholesterol-lowering properties. The effects of statins are generally attributed to a decrease in mevalonate caused by inhibition of HMG-CoA reductase, which results in an increase of nitric oxide (NO). However, a recent in vitro study demonstrated a novel effect which depended on the lipophilicity of statin and appeared to be unrelated to HMG-CoA reductase inhibition. The purpose of this study is to investigate whether the proposed mechanism actually operates in vivo. We examined the effects of simvastatin (lipophilic) and pravastatin (hydrophilic) on leukocyte behavior in a tumor necrosis factor alpha (TNFalpha)-induced leukocyte recruitment model. Leukocyte adhesion and rolling were examined in pial venules of rat brain by using confocal laser scanning microscopy after labeling leukocytes with rhodamine 6G. Experiments were conducted 4h after TNFalpha injection (0.5microg) in six groups: control, TNFalpha alone, TNFalpha + vehicle of simvastatin, TNFalpha + simvastatin (20mg/kg, 2ml/kg), TNFalpha + vehicle of pravastatin, and TNFalpha + pravastatin (40mg/kg, 2ml/kg)....Continue Reading
References
Nov 1, 1991·Microvascular Research·A VillringerK M Einhäupl
Feb 1, 1990·Nature·J L Goldstein, M S Brown
May 1, 1994·Stroke; a Journal of Cerebral Circulation·U DirnaglA Villringer
Mar 4, 1997·Circulation·G O'DriscollR R Taylor
Feb 12, 1998·The Journal of Biological Chemistry·U LaufsJ K Liao
Apr 16, 1998·Circulation·U LaufsJ K Liao
Jun 24, 1998·The Journal of Clinical Investigation·O Hernández-PereraS Lamas
Jul 22, 1998·Proceedings of the National Academy of Sciences of the United States of America·M EndresJ K Liao
Sep 3, 1998·The Journal of Biological Chemistry·U Laufs, J K Liao
Jan 20, 1999·Circulation·J F PlehnE Braunwald
Feb 6, 1999·Journal of the American College of Cardiology·W H KaesemeyerR W Caldwell
Jul 14, 1999·Circulation·A M LeferD J Lefer
Apr 25, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·M YamadaM A Moskowitz
Oct 7, 2000·Stroke; a Journal of Cerebral Circulation·U LaufsM Endres
Dec 16, 2000·The New England Journal of Medicine·A S Brett
Feb 13, 2001·Cardiovascular Research·A M LeferD J Lefer
Feb 17, 2001·The American Journal of Cardiology·R T MurphyM J Walsh
Apr 3, 2001·Stroke; a Journal of Cerebral Circulation·S Amin-HanjaniM A Moskowitz
May 22, 2001·European Journal of Vascular and Endovascular Surgery : the Official Journal of the European Society for Vascular Surgery·M JoyceD J Bouchier-Hayes
May 26, 2001·British Journal of Pharmacology·T J StalkerR Scalia
Sep 5, 2001·Circulation Research·W NiA Takeshita
Jun 5, 2002·Atherosclerosis. Supplements·James K Liao
Jul 20, 2002·International Journal of Cardiology·Enver AtalarSirri Kes
Oct 16, 2002·Circulation·Diethard PrueferMichael Buerke
Citations
Oct 21, 2006·Current Opinion in Rheumatology·Masataka Kuwana
May 22, 2009·Journal of Neurochemistry·Monica Garcia-AllozaBrian J Bacskai
Feb 1, 2006·Arthritis and Rheumatism·Aryeh M Abeles, Michael H Pillinger
Sep 27, 2012·European Journal of Preventive Cardiology·Casper N BangKristian Wachtell
Nov 3, 2010·Journal of Personality·Lauren E Duncan
Jul 28, 2019·QJM : Monthly Journal of the Association of Physicians·Hui-Chen LinNai-Wen Tsai
Apr 27, 2021·Frontiers in Pharmacology·Weilin ChenHonglin Zhu