Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infa
Authors:
Journal: Life sciences
Publication Type: Journal Article
Date: 2015
DOI: NIHMS789191
ID: 26431885
Abstract
We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondrial biogenesis and gene expression, suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a) level in the noninfarcted border zone of infarcted hearts.
Chemical List
- Cardiolipins|||Fatty Acids|||Oligopeptides|||Tissue Inhibitor of Metalloproteinase-1|||arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide|||Collagen|||Matrix Metalloproteinase 9|||Sarcoplasmic Reticulum Calcium-Transporting ATPases|||Glucose
Reference List
- Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics--2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–e220.|||Friedrich J, Apstein CS, Ingwall JS. 31P nuclear magnetic resonance spectroscopic imaging of regions of remodeled myocardium in the infarcted rat heart. Circulation. 1995;92:3527–38.|||Murray AJ, Lygate CA, Cole MA, Carr CA, Radda GK, Neubauer S, Clarke K. Insulin resistance, abnormal energy metabolism and increased ischemic damage in the chronically infarcted rat heart. Cardiovasc Res. 2006;71:149–57.|||Lionetti V, Stanley WC, Recchia FA. Modulating fatty acid oxidation in heart failure. Cardiovasc Res. 2011;90:202–9.|||Bayeva M, Gheorghiade M, Ardehali H. Mitochondria as a therapeutic target in heart failure. J Am Coll Cardiol. 2013;61:599–610.|||Ide T, Tsutsui H, Hayashidani S, Kang D, Suematsu N, Nakamura K, Utsumi H, Hamasaki N, Takeshita A. Mitochondrial DNA damage and dysfunction associated with oxidative stress in failing hearts after myocardial infarction. Circ Res. 2001;88:529–35.|||Kalsi KK, Smolenski RT, Pritchard RD, Khaghani A, Seymour AM, Yacoub MH. Energetics and function of the failing human heart with dilated or hypertrophic cardiomyopathy. Eur J Clin Invest. 1999;29:469–77.|||Szeto HH, Birk AV. Serendipity and the discovery of novel compounds that restore mitochondrial plasticity. Clinical pharmacology and therapeutics. 2014;96:672–83.|||Brown DA, Hale SL, Baines CP, Rio CL, Hamlin RL, Yueyama Y, Kijtawornrat A, Yeh ST, Frasier CR, Stewart LM, Moukdar F, Shaikh SR, Fisher-Wellman KH, Neufer PD, Kloner RA. Reduction of early reperfusion injury with the mitochondria-targeting Peptide bendavia. J Cardiovasc Pharmacol Ther. 2013;19:121–32.|||Kloner RA, Hale SL, Dai W, Gorman RC, Shuto T, Koomalsingh KJ, Gorman JH, 3rd, Sloan RC, Frasier CR, Watson CA, Bostian PA, Kypson AP, Brown DA. Reduction of ischemia/reperfusion injury with bendavia, a mitochondria-targeting cytoprotective Peptide. J Am Heart Assoc. 2012;1:e001644.|||Birk AV, Liu S, Soong Y, Mills W, Singh P, Warren JD, Seshan SV, Pardee JD, Szeto HH. The mitochondrial-targeted compound SS-31 re-energizes ischemic mitochondria by interacting with cardiolipin. Journal of the American Society of Nephrology: JASN. 2013;24:1250–61.|||Birk AV, Chao WM, Bracken C, Warren JD, Szeto HH. Targeting Mitochondrial Cardiolipin and the Cytochrome C/Cardiolipin Complex to Promote Electron Transport and Optimize Mitochondrial Atp Synthesis. Br J Pharmacol. 2013 doi: 10.1111/bph.12468.|||Szeto HH. First-In-Class Cardiolipin Therapeutic to Restore Mitochondrial Bioenergetics. Br J Pharmacol. 2013 doi: 10.1111/bph.12461.|||Siegel MP, Kruse SE, Percival JM, Goh J, White CC, Hopkins HC, Kavanagh TJ, Szeto HH, Rabinovitch PS, Marcinek DJ. Mitochondrial-targeted peptide rapidly improves mitochondrial energetics and skeletal muscle performance in aged mice. Aging cell. 2013;12:763–71.|||Zhao K, Zhao GM, Wu D, Soong Y, Birk AV, Schiller PW, Szeto HH. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J Biol Chem. 2004;279:34682–90.|||Dai W, Shi J, Gupta RC, Sabbah HN, Hale SL, Kloner RA. Bendavia, a mitochondria-targeting peptide, improves postinfarction cardiac function, prevents adverse left ventricular remodeling, and restores mitochondria-related gene expression in rats. Journal of cardiovascular pharmacology. 2014;64:543–53.|||Christie WHX. Lipid Analysis: Isolation, Separation, Identification and Lipidomic Analysis. 4. The Oily Press; Bridgwater, England: 2010.|||Yang K, Cheng H, Gross RW, Han X. Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Analytical chemistry. 2009;81:4356–68.|||Huss JM, Kelly DP. Mitochondrial energy metabolism in heart failure: a question of balance. J Clin Invest. 2005;115:547–55.|||Rowe GC, Jiang A, Arany Z. PGC-1 coactivators in cardiac development and disease. Circ Res. 2010;107:825–38.|||De Vos KJ, Allan VJ, Grierson AJ, Sheetz MP. Mitochondrial function and actin regulate dynamin-related protein 1-dependent mitochondrial fission. Current biology: CB. 2005;15:678–83.|||Kubli DA, Zhang X, Lee Y, Hanna RA, Quinsay MN, Nguyen CK, Jimenez R, Petrosyan S, Murphy AN, Gustafsson AB. Parkin protein deficiency exacerbates cardiac injury and reduces survival following myocardial infarction. J Biol Chem. 2013;288:915–26.|||Sparagna GC, Chicco AJ, Murphy RC, Bristow MR, Johnson CA, Rees ML, Maxey ML, McCune SA, Moore RL. Loss of cardiac tetralinoleoyl cardiolipin in human and experimental heart failure. Journal of lipid research. 2007;48:1559–70.|||Chicco AJ, Sparagna GC. Role of cardiolipin alterations in mitochondrial dysfunction and disease. American journal of physiology Cell physiology. 2007;292:C33–44.|||Spinale FG. Matrix metalloproteinases: regulation and dysregulation in the failing heart. Circ Res. 2002;90:520–30.|||Bers DM. Altered cardiac myocyte Ca regulation in heart failure. Physiology (Bethesda) 2006;21:380–7.|||Schwartz Longacre L, Kloner RA, Arai AE, Baines CP, Bolli R, Braunwald E, Downey J, Gibbons RJ, Gottlieb RA, Heusch G, Jennings RB, Lefer DJ, Mentzer RM, Murphy E, Ovize M, Ping P, Przyklenk K, Sack MN, Vander Heide RS, Vinten-Johansen J, Yellon DM. New horizons in cardioprotection: recommendations from the 2010 National Heart, Lung, and Blood Institute Workshop. Circulation. 2011;124:1172–9.|||Menees DS, Peterson ED, Wang Y, Curtis JP, Messenger JC, Rumsfeld JS, Gurm HS. Door-to-balloon time and mortality among patients undergoing primary PCI. The New England journal of medicine. 2013;369:901–9.|||Adlam VJ, Harrison JC, Porteous CM, James AM, Smith RA, Murphy MP, Sammut IA. Targeting an antioxidant to mitochondria decreases cardiac ischemia-reperfusion injury. FASEB J. 2005;19:1088–95.|||Murphy MP, Smith RA. Targeting antioxidants to mitochondria by conjugation to lipophilic cations. Annu Rev Pharmacol Toxicol. 2007;47:629–56.|||Reily C, Mitchell T, Chacko BK, Benavides G, Murphy MP, Darley-Usmar V. Mitochondrially targeted compounds and their impact on cellular bioenergetics. Redox Biol. 2013;1:86–93.|||Sloan RC, Moukdar F, Frasier CR, Patel HD, Bostian PA, Lust RM, Brown DA. Mitochondrial permeability transition in the diabetic heart: contributions of thiol redox state and mitochondrial calcium to augmented reperfusion injury. J Mol Cell Cardiol. 2012;52:1009–18.|||Beer M, Seyfarth T, Sandstede J, Landschutz W, Lipke C, Kostler H, von Kienlin M, Harre K, Hahn D, Neubauer S. Absolute concentrations of high-energy phosphate metabolites in normal, hypertrophied, and failing human myocardium measured noninvasively with (31)P-SLOOP magnetic resonance spectroscopy. J Am Coll Cardiol. 2002;40:1267–74.|||Jarreta D, Orus J, Barrientos A, Miro O, Roig E, Heras M, Moraes CT, Cardellach F, Casademont J. Mitochondrial function in heart muscle from patients with idiopathic dilated cardiomyopathy. Cardiovasc Res. 2000;45:860–5.|||Buchwald A, Till H, Unterberg C, Oberschmidt R, Figulla HR, Wiegand V. Alterations of the mitochondrial respiratory chain in human dilated cardiomyopathy. Eur Heart J. 1990;11:509–16.|||Russell LK, Finck BN, Kelly DP. Mouse models of mitochondrial dysfunction and heart failure. J Mol Cell Cardiol. 2005;38:81–91.|||Russell LK, Mansfield CM, Lehman JJ, Kovacs A, Courtois M, Saffitz JE, Medeiros DM, Valencik ML, McDonald JA, Kelly DP. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res. 2004;94:525–33.|||Shi J, Jiang B, Qiu Y, Guan J, Jain M, Cao X, Bauer M, Su L, Burkly LC, Leone TC, Kelly DP, Liao R. PGC1alpha plays a critical role in TWEAK-induced cardiac dysfunction. PLoS One. 2013;8:e54054.|||Arany Z, He H, Lin J, Hoyer K, Handschin C, Toka O, Ahmad F, Matsui T, Chin S, Wu PH, Rybkin II, Shelton JM, Manieri M, Cinti S, Schoen FJ, Bassel-Duby R, Rosenzweig A, Ingwall JS, Spiegelman BM. Transcriptional coactivator PGC-1 alpha controls the energy state and contractile function of cardiac muscle. Cell Metab. 2005;1:259–71.|||Ferre P. The biology of peroxisome proliferator-activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes. 2004;53(Suppl 1):S43–50.|||Razeghi P, Young ME, Abbasi S, Taegtmeyer H. Hypoxia in vivo decreases peroxisome proliferator-activated receptor alpha-regulated gene expression in rat heart. Biochem Biophys Res Commun. 2001;287:5–10.|||Sack MN, Rader TA, Park S, Bastin J, McCune SA, Kelly DP. Fatty acid oxidation enzyme gene expression is downregulated in the failing heart. Circulation. 1996;94:2837–42.|||Kim EH, Tolhurst AT, Szeto HH, Cho SH. Targeting CD36-mediated inflammation reduces acute brain injury in transient, but not permanent, ischemic stroke. CNS neuroscience & therapeutics. 2015;21:385–91.|||Cho S, Szeto HH, Kim E, Kim H, Tolhurst AT, Pinto JT. A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. J Biol Chem. 2007;282:4634–42.|||Sack MN, Kelly DP. The energy substrate switch during development of heart failure: gene regulatory mechanisms (Review) Int J Mol Med. 1998;1:17–24.|||Eirin A, Williams BJ, Ebrahimi B, Zhang X, Crane JA, Lerman A, Textor SC, Lerman LO. Mitochondrial targeted peptides attenuate residual myocardial damage after reversal of experimental renovascular hypertension. Journal of hypertension. 2014;32:154–65.|||Bers DM, Despa S, Bossuyt J. Regulation of Ca2+ and Na+ in normal and failing cardiac myocytes. Ann N Y Acad Sci. 2006;1080:165–77.|||Lipskaia L, Chemaly ER, Hadri L, Lompre AM, Hajjar RJ. Sarcoplasmic reticulum Ca(2+) ATPase as a therapeutic target for heart failure. Expert Opin Biol Ther. 2010;10:29–41.|||Periasamy M, Huke S. SERCA pump level is a critical determinant of Ca(2+)homeostasis and cardiac contractility. J Mol Cell Cardiol. 2001;33:1053–63.|||Cleutjens JP, Kandala JC, Guarda E, Guntaka RV, Weber KT. Regulation of collagen degradation in the rat myocardium after infarction. J Mol Cell Cardiol. 1995;27:1281–92.|||Tyagi SC, Kumar SG, Haas SJ, Reddy HK, Voelker DJ, Hayden MR, Demmy TL, Schmaltz RA, Curtis JJ. Post-transcriptional regulation of extracellular matrix metalloproteinase in human heart end-stage failure secondary to ischemic cardiomyopathy. J Mol Cell Cardiol. 1996;28:1415–28.|||Rohde LE, Ducharme A, Arroyo LH, Aikawa M, Sukhova GH, Lopez-Anaya A, McClure KF, Mitchell PG, Libby P, Lee RT. Matrix metalloproteinase inhibition attenuates early left ventricular enlargement after experimental myocardial infarction in mice. Circulation. 1999;99:3063–70.|||Ducharme A, Frantz S, Aikawa M, Rabkin E, Lindsey M, Rohde LE, Schoen FJ, Kelly RA, Werb Z, Libby P, Lee RT. Targeted deletion of matrix metalloproteinase-9 attenuates left ventricular enlargement and collagen accumulation after experimental myocardial infarction. J Clin Invest. 2000;106:55–62.|||Heymans S, Luttun A, Nuyens D, Theilmeier G, Creemers E, Moons L, Dyspersin GD, Cleutjens JP, Shipley M, Angellilo A, Levi M, Nube O, Baker A, Keshet E, Lupu F, Herbert JM, Smits JF, Shapiro SD, Baes M, Borgers M, Collen D, Daemen MJ, Carmeliet P. Inhibition of plasminogen activators or matrix metalloproteinases prevents cardiac rupture but impairs therapeutic angiogenesis and causes cardiac failure. Nat Med. 1999;5:1135–42.|||Dai DF, Hsieh EJ, Chen T, Menendez LG, Basisty NB, Tsai L, Beyer RP, Crispin DA, Shulman NJ, Szeto HH, Tian R, MacCoss MJ, Rabinovitch PS. Global proteomics and pathway analysis of pressure-overload-induced heart failure and its attenuation by mitochondrial-targeted peptides. Circ Heart Fail. 2013;6:1067–76.