Circulation. 2002;105:868-873
Published online before print January 14, 2002, doi: 10.1161/hc0702.104164
Published online before print January 14, 2002, doi: 10.1161/hc0702.104164
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Circulation. 2002;105:868.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Fluvastatin, a 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitor, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction
From the Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Correspondence to Hiroyuki Tsutsui, MD, PhD, Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan. E-mail prehiro{at}cardiol.med.kyushu-u.ac.jp
Background— Short-term administration of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, statins, has been shown to attenuate ischemia-reperfusion injury. However, the effects of long-term administration of statins on left ventricular (LV) remodeling and failure after myocardial infarction remain unknown.
Methods and Results— Mice were subjected to coronary artery ligation and were treated for 4 weeks with vehicle or fluvastatin (10 mg/kg per day PO). Fluvastatin increased survival (61% versus 86%; P<0.05) without affecting the infarct size (52±2% versus 49±3%; P=NS). Fluvastatin not only attenuated LV dilatation but also decreased LV end-diastolic pressure and lung weight. Furthermore, it reduced cardiac myocyte hypertrophy and interstitial fibrosis of the noninfarcted LV and also improved LV ejection performance. LV matrix metalloproteinase (MMP)-2 and MMP-13 were increased in myocardial infarction, which was attenuated in fluvastatin-treated mice.
Conclusions— Fluvastatin increased survival in a murine model of postinfarct heart failure, which was associated with the amelioration of LV structural remodeling and contractile failure. Moreover, these effects were associated with the attenuation of increased MMP activity. Thus, long-term treatment with fluvastatin might be beneficial also in patients with heart failure and might improve their long-term survival.
Key Words: cholesterol • metalloproteinases • heart failure • myocardial infarction • remodeling
This article has been cited by other articles:
 |
|
 |
|
  V. Zaca, S. Rastogi, M. Imai, M. Wang, V. G. Sharov, A. Jiang, S. Goldstein, and H. N. Sabbah Chronic Monotherapy With Rosuvastatin Prevents Progressive Left Ventricular Dysfunction and Remodeling in Dogs With Heart Failure J. Am. Coll. Cardiol., August 7, 2007; 50(6): 551 - 557. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Afilalo, A. A Majdan, and M. J Eisenberg Intensive statin therapy in acute coronary syndromes and stable coronary heart disease: a comparative meta-analysis of randomised controlled trials Heart, August 1, 2007; 93(8): 914 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Ruperez, R. Rodrigues-Diez, L. M. Blanco-Colio, E. Sanchez-Lopez, J. Rodriguez-Vita, V. Esteban, G. Carvajal, J. J. Plaza, J. Egido, and M. Ruiz-Ortega HMG-CoA Reductase Inhibitors Decrease Angiotensin II-Induced Vascular Fibrosis: Role of RhoA/ROCK and MAPK Pathways Hypertension, August 1, 2007; 50(2): 377 - 383. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. K. Khush, D. D. Waters, V. Bittner, P. C. Deedwania, J. J.P. Kastelein, S. J. Lewis, and N. K. Wenger Effect of High-Dose Atorvastatin on Hospitalizations for Heart Failure: Subgroup Analysis of the Treating to New Targets (TNT) Study Circulation, February 6, 2007; 115(5): 576 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. M. Greer, A. K. Kakkar, J. W. Elrod, L. J. Watson, S. P. Jones, and D. J. Lefer Low-dose simvastatin improves survival and ventricular function via eNOS in congestive heart failure Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2743 - H2751. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Bauersachs, K. Hiss, D. Fraccarollo, U. Laufs, and H. Ruetten Simvastatin improves left ventricular function after myocardial infarction in hypercholesterolemic rabbits by anti-inflammatory effects Cardiovasc Res, December 1, 2006; 72(3): 438 - 446. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A F Leite-Moreira and P Castro-Chaves Heart failure: statins for all? Heart, November 1, 2006; 92(11): 1537 - 1538. [Full Text] [PDF]
|
|
|
|
|
|
P. van der Harst, A. A. Voors, W. H. van Gilst, M. Bohm, and D. J. van Veldhuisen Statins in the treatment of chronic heart failure: Biological and clinical considerations Cardiovasc Res, August 1, 2006; 71(3): 443 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Custodis, M. Eberl, H. Kilter, M. Bohm, and U. Laufs Association of RhoGDI{alpha} with Rac1 GTPase mediates free radical production during myocardial hypertrophy Cardiovasc Res, July 15, 2006; 71(2): 342 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Foody, R. Shah, D. Galusha, F. A. Masoudi, E. P. Havranek, and H. M. Krumholz Statins and Mortality Among Elderly Patients Hospitalized With Heart Failure Circulation, February 28, 2006; 113(8): 1086 - 1092. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Ichihara, A. Noda, K. Nagata, K. Obata, J. Xu, G. Ichihara, S. Oikawa, S. Kawanishi, Y. Yamada, and M. Yokota Pravastatin increases survival and suppresses an increase in myocardial matrix metalloproteinase activity in a rat model of heart failure Cardiovasc Res, February 15, 2006; 69(3): 726 - 735. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ramasubbu and D. L. Mann The Emerging Role of Statins in the Treatment of Heart Failure J. Am. Coll. Cardiol., January 17, 2006; 47(2): 342 - 344. [Full Text] [PDF]
|
|
|
|
|
|
S. Sola, M. Q.S. Mir, S. Lerakis, N. Tandon, and B. V. Khan Atorvastatin Improves Left Ventricular Systolic Function and Serum Markers of Inflammation in Nonischemic Heart Failure J. Am. Coll. Cardiol., January 17, 2006; 47(2): 332 - 337. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Sakai, Y. Hirooka, H. Shigematsu, T. Kishi, K. Ito, H. Shimokawa, A. Takeshita, and K. Sunagawa Overexpression of eNOS in brain stem reduces enhanced sympathetic drive in mice with myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2005; 289(5): H2159 - H2166. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Senthil, S. N. Chen, N. Tsybouleva, T. Halder, S. F. Nagueh, J. T. Willerson, R. Roberts, and A.J. Marian Prevention of Cardiac Hypertrophy by Atorvastatin in a Transgenic Rabbit Model of Human Hypertrophic Cardiomyopathy Circ. Res., August 5, 2005; 97(3): 285 - 292. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Fukuta, D. C. Sane, S. Brucks, and W. C. Little Statin Therapy May Be Associated With Lower Mortality in Patients With Diastolic Heart Failure: A Preliminary Report Circulation, July 19, 2005; 112(3): 357 - 363. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. B. Keller and L. Lemberg Statin Therapy in Congestive Heart Failure Am. J. Crit. Care., July 1, 2005; 14(4): 338 - 340. [Full Text] [PDF]
|
|
|
|
|
|
T.-M. Lee, M.-S. Lin, T.-F. Chou, C.-H. Tsai, and N.-C. Chang Effect of pravastatin on development of left ventricular hypertrophy in spontaneously hypertensive rats Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H220 - H227. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A D Gavin and A D Struthers Allopurinol reduces B-type natriuretic peptide concentrations and haemoglobin but does not alter exercise capacity in chronic heart failure Heart, June 1, 2005; 91(6): 749 - 753. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Ertl and S. Frantz Healing after myocardial infarction Cardiovasc Res, April 1, 2005; 66(1): 22 - 32. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. O'Neil-Callahan, G. Katsimaglis, M. R. Tepper, J. Ryan, C. Mosby, J. P.A. Ioannidis, and P. G. Danias Statins decrease perioperative cardiac complications in patients undergoing noncardiac vascular surgery: The Statins for Risk Reduction in Surgery (StaRRS) study J. Am. Coll. Cardiol., February 1, 2005; 45(3): 336 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. G. Ray, Y. Gong, K. Sykora, and J. V. Tu Statin Use and Survival Outcomes in Elderly Patients With Heart Failure Arch Intern Med, January 10, 2005; 165(1): 62 - 67. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Porter, N. A. Turner, D. J. O'Regan, and S. G. Ball Tumor necrosis factor {alpha} induces human atrial myofibroblast proliferation, invasion and MMP-9 secretion: inhibition by simvastatin Cardiovasc Res, December 1, 2004; 64(3): 507 - 515. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Landmesser, N. Engberding, F. H. Bahlmann, A. Schaefer, A. Wiencke, A. Heineke, S. Spiekermann, D. Hilfiker-Kleiner, C. Templin, D. Kotlarz, et al. Statin-Induced Improvement of Endothelial Progenitor Cell Mobilization, Myocardial Neovascularization, Left Ventricular Function, and Survival After Experimental Myocardial Infarction Requires Endothelial Nitric Oxide Synthase Circulation, October 5, 2004; 110(14): 1933 - 1939. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Liao, M. Asakura, S. Takashima, A. Ogai, Y. Asano, Y. Shintani, T. Minamino, H. Asanuma, S. Sanada, J. Kim, et al. Celiprolol, A Vasodilatory {beta}-Blocker, Inhibits Pressure Overload-Induced Cardiac Hypertrophy and Prevents the Transition to Heart Failure via Nitric Oxide-Dependent Mechanisms in Mice Circulation, August 10, 2004; 110(6): 692 - 699. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kaikita, T. Hayasaki, T. Okuma, W. A. Kuziel, H. Ogawa, and M. Takeya Targeted Deletion of CC Chemokine Receptor 2 Attenuates Left Ventricular Remodeling after Experimental Myocardial Infarction Am. J. Pathol., August 1, 2004; 165(2): 439 - 447. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ito, T. Adachi, D. R. Pimentel, Y. Ido, and W. S. Colucci Statins Inhibit {beta}-Adrenergic Receptor-Stimulated Apoptosis in Adult Rat Ventricular Myocytes via a Rac1-Dependent Mechanism Circulation, July 27, 2004; 110(4): 412 - 418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Spencer, J. Allegrone, R. J. Goldberg, J. M. Gore, K. A.A. Fox, C. B. Granger, R. H. Mehta, D. Brieger, and the GRACE Investigators* Association of Statin Therapy with Outcomes of Acute Coronary Syndromes: The GRACE Study Ann Intern Med, June 1, 2004; 140(11): 857 - 866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. Schonbeck and P. Libby Inflammation, Immunity, and HMG-CoA Reductase Inhibitors: Statins as Antiinflammatory Agents? Circulation, June 1, 2004; 109(21_suppl_1): II-18 - II-26. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hattori, H. Shimokawa, M. Higashi, J. Hiroki, Y. Mukai, H. Tsutsui, K. Kaibuchi, and A. Takeshita Long-Term Inhibition of Rho-Kinase Suppresses Left Ventricular Remodeling After Myocardial Infarction in Mice Circulation, May 11, 2004; 109(18): 2234 - 2239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Frey, H. A. Katus, E. N. Olson, and J. A. Hill Hypertrophy of the Heart: A New Therapeutic Target? Circulation, April 6, 2004; 109(13): 1580 - 1589. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Porter, N. A. Turner, D. J. O'Regan, A. J. Balmforth, and S. G. Ball Simvastatin reduces human atrial myofibroblast proliferation independently of cholesterol lowering via inhibition of RhoA Cardiovasc Res, March 1, 2004; 61(4): 745 - 755. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. B. Horwich, W. R. MacLellan, and G. C. Fonarow Statin therapy is associated with improved survival in ischemic and non-ischemic heart failure J. Am. Coll. Cardiol., February 18, 2004; 43(4): 642 - 648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Varela and J. L. Garvin Acute and Chronic Regulation of Thick Ascending Limb Endothelial Nitric Oxide Synthase by Statins J. Am. Soc. Nephrol., February 1, 2004; 15(2): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Takeshita, M. Hayashi, S. Iino, T. Kondo, Y. Inden, M. Iwase, T. Kojima, M. Hirai, M. Ito, D. J. Loskutoff, et al. Increased Expression of Plasminogen Activator Inhibitor-1 in Cardiomyocytes Contributes to Cardiac Fibrosis after Myocardial Infarction Am. J. Pathol., February 1, 2004; 164(2): 449 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Huang, K.E. Walker, F. Hanley, J. Narula, S.R. Houser, and T.N. Tulenko Cardiac Systolic and Diastolic Dysfunction After a Cholesterol-Rich Diet Circulation, January 6, 2004; 109(1): 97 - 102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. A. Woodcock Unc-II and Unc-III Are Cardioprotective against Ischemia Reperfusion Injury: An Essential Endogenous Cardioprotective Role for CRFR2 in the Murine Heart Endocrinology, January 1, 2004; 145(1): 21 - 23. [Full Text] [PDF]
|
|
|
|
|
|
S. Hayashidani, H. Tsutsui, T. Shiomi, M. Ikeuchi, H. Matsusaka, N. Suematsu, J. Wen, K. Egashira, and A. Takeshita Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction Circulation, October 28, 2003; 108(17): 2134 - 2140. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Hayashidani, H. Tsutsui, M. Ikeuchi, T. Shiomi, H. Matsusaka, T. Kubota, K. Imanaka-Yoshida, T. Itoh, and A. Takeshita Targeted deletion of MMP-2 attenuates early LV rupture and late remodeling after experimental myocardial infarction Am J Physiol Heart Circ Physiol, August 7, 2003; 285(3): H1229 - H1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. P. Anderson Lipid-lowering therapy for prevention of ventricular tachyarrhythmias J. Am. Coll. Cardiol., July 2, 2003; 42(1): 88 - 92. [Full Text] [PDF]
|
|
|
|
|
|
T. Shiomi, H. Tsutsui, M. Ikeuchi, H. Matsusaka, S. Hayashidani, N. Suematsu, J. Wen, T. Kubota, and A. Takeshita Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction J. Am. Coll. Cardiol., July 2, 2003; 42(1): 165 - 172. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. E. J. M. Creemers, J. N. Davis, A. M. Parkhurst, P. Leenders, K. B. Dowdy, E. Hapke, A. M. Hauet, P. G. Escobar, J. P. M. Cleutjens, J. F. M. Smits, et al. Deficiency of TIMP-1 exacerbates LV remodeling after myocardial infarction in mice Am J Physiol Heart Circ Physiol, January 1, 2003; 284(1): H364 - H371. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Shiomi, H. Tsutsui, S. Hayashidani, N. Suematsu, M. Ikeuchi, J. Wen, M. Ishibashi, T. Kubota, K. Egashira, and A. Takeshita Pioglitazone, a Peroxisome Proliferator-Activated Receptor-{gamma} Agonist, Attenuates Left Ventricular Remodeling and Failure After Experimental Myocardial Infarction Circulation, December 10, 2002; 106(24): 3126 - 3132. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Zeuke, A. J Ulmer, S. Kusumoto, H. A Katus, and H. Heine TLR4-mediated inflammatory activation of human coronary artery endothelial cells by LPS Cardiovasc Res, October 1, 2002; 56(1): 126 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. M. Thompson and I. B. Squire Matrix metalloproteinase-9 expression after myocardial infarction: physiological or pathological? Cardiovasc Res, June 1, 2002; 54(3): 495 - 498. [Full Text] [PDF]
|
|
|
|
|
|
H. Krum and J. J. McMurray Statins and chronic heart failure: do we need a large-scale outcome trial? J. Am. Coll. Cardiol., May 15, 2002; 39(10): 1567 - 1573. [Abstract] [Full Text] [PDF]
|
|