PMID: 11922901Mar 30, 2002Paper

Impact of HMG CoA reductase inhibition on small GTPases in the heart

Cardiovascular Research
Ulrich LaufsGeorg Nickenig

Abstract

Members of the Rho GTPase family, Rac1 and RhoA have been suggested to be mediators of cardiac hypertrophy in mice. Rho proteins are posttranslationally isoprenylated. In addition to cholesterol-lowering, statins inhibit the isoprenylation of small G proteins. Therefore, it was tested if these drugs inhibit Rac1 and RhoA activity in cardiomyocytes and, thereby, prevent angiotensin II-mediated expression of atrial natriuretic factor (ANF) and myosin light chain (MLC)-2 in the heart. Western and Northern analysis of rat neonatal cardiomyocytes and H9C2 cells showed inhibition of basal and angiotensin-stimulated Rac1 expression, membrane-translocation and activity after statin treatment. Similarly, basal and stimulated RhoA membrane expression was inhibited. Statins concentration- and time-dependently downregulated basal as well as angiotensin-induced expression of ANF by 86+/-2.3% and 89+/-1.7%, as well as MLC-2 by 75+/-4.1% and 84+/-6%, respectively. Direct inhibition of Rac GTPase by overexpression of the dominant negative mutant RacN17 or by Clostridium sordellii lethal toxin in rat H9C2 cells inhibited ANF expression by 70+/-4.9% and 78+/-10%, respectively. Inhibition of RhoA by Clostridium botulinum C3 transferase or the dom...Continue Reading

Citations

Aug 2, 2008·Archives of Toxicology·Oliver Adam, Ulrich Laufs
Aug 9, 2007·Cardiovascular Drugs and Therapy·Teruo Inoue, Koichi Node
Aug 13, 2003·Current Atherosclerosis Reports·Ulrich Laufs, James K Liao
Dec 10, 2003·Current Atherosclerosis Reports·Jean Davignon
Feb 21, 2009·Current Atherosclerosis Reports·Kumudha Ramasubbu, John A Farmer
Jun 9, 2005·Atherosclerosis·Kensaku MaedaMasayasu Inoue
Mar 9, 2005·Biochemical and Biophysical Research Communications·Pascal SirventAlain Lacampagne
Jan 21, 2004·The Journal of Surgical Research·Tushar R Patel, Siobhan A Corbett
Jul 2, 2011·Expert Reviews in Molecular Medicine·Karen E Porter, Neil A Turner
Mar 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Manish RauthanMarc Pilon
Mar 25, 2009·Antioxidants & Redox Signaling·Masuko Ushio-Fukai, Norifumi Urao
Jan 11, 2012·Antioxidants & Redox Signaling·Sanja CosoStavros Selemidis
Feb 13, 2010·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Mahesh ShivannaSangly P Srinivas
Mar 10, 2010·Cardiovascular Research·Jan-Christian ReilHans-Ruprecht Neuberger
Dec 2, 2009·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Eun Hui BaeSoo Wan Kim
Apr 12, 2005·Annual Review of Pharmacology and Toxicology·James K Liao, Ulrich Laufs
Jan 14, 2003·Annual Review of Physiology·N Frey, E N Olson
Jul 28, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Vincent G DeMarcoKevin C Dellsperger
May 4, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Shin-ichi TanakaHiroaki Shimokawa
Nov 25, 2003·American Journal of Respiratory Cell and Molecular Biology·Jeffrey R JacobsonJoe G N Garcia
Jul 22, 2006·American Journal of Respiratory Cell and Molecular Biology·Naoya TakedaHiroaki Kume
Dec 9, 2008·Circulation Journal : Official Journal of the Japanese Circulation Society·Mamunur RashidHiroaki Shimokawa
Apr 29, 2010·Circulation Journal : Official Journal of the Japanese Circulation Society·Qian Zhou, James K Liao
May 3, 2011·Circulation Journal : Official Journal of the Japanese Circulation Society·Takuya Kishi
Jun 29, 2013·Vascular Health and Risk Management·Kwadwo Osei BonsuDaniel Diamond Reidpath
Aug 8, 2013·Antioxidants & Redox Signaling·Oliver Adam, Ulrich Laufs
May 3, 2006·Proceedings of the National Academy of Sciences of the United States of America·Minoru SatohJames K Liao
Apr 2, 2005·Zeitschrift für Kardiologie·M BöhmD J van Veldhuisen
Jul 5, 2012·Basic Research in Cardiology·Oliver AdamUlrich Laufs
Nov 13, 2008·The Journal of Physiology·Joanne E MallinsonPaul L Greenhaff
Jun 7, 2012·Journal of Molecular and Cellular Cardiology·Anne ReboulleauNatalie Fournier
Jun 28, 2012·Biochimica Et Biophysica Acta·Yoh TakuwaKazuaki Yoshioka
Apr 15, 2008·Cancer Letters·Masuko Ushio-Fukai, Yoshimasa Nakamura
Mar 15, 2008·Journal of Molecular and Cellular Cardiology·Frank Lezoualc'hEric Morel

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