Abstract
Background
Oxidative stress is involved in progression of left ventricular hypertrophy and heart failure. Since NADPH oxidases are a major source of reactive oxygen species in the heart, we studied left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91phox.
Methods and results
gp91phox knockout (KO) and wild–type (WT) animals underwent coronary artery ligation. Mortality was significant higher in the gp91phox KO mice. However, transthoracic echocardiography performed at days 1, 7, and 56 at mid–papillary levels revealed that progression of left ventricular remodeling was not influenced by the genotype. Moreover, systemic oxidative stress was not reduced in gp91phox KO mice as indicated by a significant increase in lipid peroxides potentially mediated by an increase of the NADPH subunit nox–1 in gp91phox KO mice.
Conclusion
Targeted deletion of the NADPH subunit gp91phox does not affect left ventricular remodeling following myocardial infarction and does not decrease the production of oxidative stress. However, the final role of the different NADPH subunits in the heart under pathophysiologic conditions remains to be determined.
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References
Bauersachs J, Galuppo P, Fraccarollo D, Christ M, Ertl G (2001) Improvement of left ventricular remodeling and function by hydroxymethylglutaryl coenzyme a reductase inhibition with cerivastatin in rats with heart failure after myocardial infarction. Circulation 104:982–985
Bendall JK, Cave AC, Heymes C, Gall N, Shah AM (2002) Pivotal role of a gp91 (phox)–containing NADPH oxidase in angiotensin II–induced cardiac hypertrophy in mice. Circulation 105:293–296
Byrne JA, Grieve DJ, Bendall JK, Li JM, Gove C, Lambeth JD, Cave AC, Shah AM (2003) Contrasting roles of NADPH oxidase isoforms in pressure–overload versus angiotensin II–induced cardiac hypertrophy. Circ Res 93:802–805
Byrne JA, Grieve DJ, Cave AC, Shah AM (2003) Oxidative stress and heart failure. Arch Mal Coeur Vaiss 96:214–221
Chien KR (1999) Stress pathways and heart failure. Cell 98:555–558
Dhalla AK, Hill MF, Singal PK (1996) Role of oxidative stress in transition of hypertrophy to heart failure. J Am Coll Cardiol 28:506–514
Engberding N, Spiekermann S, Schaefer A, Heineke A, Wiencke A, Muller M, Fuchs M, Hilfiker–Kleiner D, Hornig B, Drexler H, Landmesser U (2004) Allopurinol attenuates left ventricular remodeling and dysfunction after experimental myocardial infarction: a new action for an old drug? Circulation 110:2175–2179
Frantz S, Calvillo L, Tillmanns J, Elbing I, Dienesch C, Bischoff H, Ertl G, Bauersachs J (2005) Repetitive postprandial hyperglycemia increases cardiac ischemia/ reperfusion injury. Prevention by the alpha–Glucosidase Inhibitor Acarbose. FASEB 19:591–593
Frantz S, Hu K, Widder J, Bayer B, Witzel CC, Schmidt I, Galuppo P, Strotmann J, Ertl G, Bauersachs J (2004) Peroxisome proliferator activated–receptor agonism and left ventricular remodeling in mice with chronic myocardial infarction. Br J Pharmacol 141:9–14
Frantz S, Kobzik L, Kim YD, Fukazawa R, Medzhitov R, Lee RT, Kelly RA (1999) Toll4 (TLR4) expression in cardiac myocytes in normal and failing myocardium. J Clin Invest 104:271–280
Fukui T, Yoshiyama M, Hanatani A, Omura T, Yoshikawa J, Abe Y (2001) Expression of p22–phox and gp91–phox, essential components of NADPH oxidase, increases after myocardial infarction. Biochem Biophys Res Commun 281:1200–1206
Gehrmann J, Frantz S, Maguire CT, Vargas M, Ducharme A, Wakimoto H, Lee RT, Berul CI (2001) Electrophysiological characterization of murine myocardial ischemia and infarction. Basic Res Cardiol 96:237–250
Griendling KK, Sorescu D, Ushio–Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86:494–501
Grieve DJ, Shah AM (2003) Oxidative stress in heart failure. More than just damage. Eur Heart J 24:2161–2163
Heymes C, Bendall JK, Ratajczak P, Cave AC, Samuel JL, Hasenfuss G, Shah AM (2003) Increased myocardial NADPH oxidase activity in human heart failure. J Am Coll Cardiol 41:2164–2171
Josephson RA, Silverman HS, Lakatta EG, Stern MD, Zweier JL (1991) Study of the mechanisms of hydrogen peroxide and hydroxyl free radical–induced cellular injury and calcium overload in cardiac myocytes. J Biol Chem 266:2354–2361
Kinugawa S, Tsutsui H, Hayashidani S, Ide T, Suematsu N, Satoh S, Utsumi H, Takeshita A (2000) Treatment with dimethylthiourea prevents left ventricular remodeling and failure after experimental myocardial infarction in mice: role of oxidative stress. Circ Res 87:392–398
Kinugawa S, Zhang J, Messina E, Walsh E, Huang H, Kaminski PM, Wolin MS, Hintze TH (2005) gp91phox–containing NAD(P)H oxidase mediates attenuation of nitric oxide–dependent control of myocardial oxygen consumption by ANG II. Am J Physiol Heart Circ Physiol 289:H862–H867
Lassegue B, Clempus RE (2003) Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285:R277–R297
Li JM, Gall NP, Grieve DJ, Chen M, Shah AM (2002) Activation of NADPH oxidase during progression of cardiac hypertrophy to failure. Hypertension 40:477–484
Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U (2003) Oxygen free radical release in human failing myocardium is associated with increased activity of rac1–GTPase and represents a target for statin treatment. Circulation 108:1567–1574
Maytin M, Siwik DA, Ito M, Xiao L, Sawyer DB, Liao R, Colucci WS (2004) Pressure overload–induced myocardial hypertrophy in mice does not require gp91phox. Circulation 109:1168–1171
Pollock JD, Williams DA, Gifford MA, Li LL, Du X, Fisherman J, Orkin SH, Doerschuk CM, Dinauer MC (1995) Mouse model of X–linked chronic granulomatous disease, an inherited defect in phagocyte superoxide production. Nat Genet 9:202–209
Shiomi T, Tsutsui H, Matsusaka H, Murakami K, Hayashidani S, Ikeuchi M, Wen J, Kubota T, Utsumi H, Takeshita A (2004) Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice. Circulation 109:544–549
Ushio–Fukai M, Tang Y, Fukai T, Dikalov SI, Ma Y, Fujimoto M, Quinn MT, Pagano PJ, Johnson C, Alexander RW (2002) Novel role of gp91(phox)–containing NAD(P)H oxidase in vascular endothelial growth factor–induced signaling and angiogenesis. Circ Res 91:1160–1167
Wong SH, Knight JA, Hopfer SM, Zaharia O, Leach CN Jr, Sunderman FW Jr (1987) Lipoperoxides in plasma as measured by liquid–chromatographic separation of malondialdehyde–thiobarbituric acid adduct. Clin Chem 33:214–220
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Frantz, S., Brandes, R.P., Hu, K. et al. Left ventricular remodeling after myocardial infarction in mice with targeted deletion of the NADPH oxidase subunit gp91PHOX. Basic Res Cardiol 101, 127–132 (2006). https://doi.org/10.1007/s00395-005-0568-x
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DOI: https://doi.org/10.1007/s00395-005-0568-x