Journal of Cardiovascular Pharmacology and Therapeutics

 

Advanced Search

Journal Navigation

Journal Home

Subscriptions

Archive

Contact Us

Table of Contents

Register here to gain access to SAGE's 500+ Journals Online

Click here to sign up for SAGE Journal Email Alerts today!

Sign In to gain access to subscriptions and/or personal tools.
This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nordlie, M. A.
Right arrow Articles by Kloner, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nordlie, M. A.
Right arrow Articles by Kloner, R. A.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 11, No. 1, 17-30 (2006)
DOI: 10.1177/107424840601100102

Molecular Aspects of Ischemic Heart Disease: Ischemia/Reperfusion–Induced Genetic Changes and Potential Applications of Gene and RNA Interference Therapy

Margaret A. Nordlie, DA

Division of Mathematics and Natural Sciences, University of Mary, Bismarck, ND

Loren E. Wold, PhD

Boris Z. Simkhovich, MD, PhD

Casilde Sesti, PhD

The Heart Institute, Good Samaritan Hospital, University of Southern California, Los Angeles, CA.

Robert A. Kloner, MD, PhD

University of Southern California; The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017; rkloner{at}goodsam.org

Molecular biologic techniques have a variety of applications in the study of ischemic heart disease, including roles in elucidating cardiac genetic changes resulting from ischemia as well as in developing therapeutic interventions to treat ischemic heart disease. This review describes recent studies documenting genetic changes associated with myocardial ischemia and infarction as well as those investigating the safety and effectiveness of gene therapy for stimulating angiogenesis, protecting the heart against reperfusion injury, and treating heart failure. Also discussed are future research directions, including the potential use of RNA interference and combined stem cell therapy and gene therapy for the treatment of cardiovascular disease.

Key Words: ischemia • genetics • gene therapy • angiogenesis • cardioprotection • heart failure

References

  • Simkhovich BZ, Marjoram P, Poizat C, et al. Brief episode of ischemia activates protective genetic program in rat heart: A gene chip study. Cardiovasc Res 59:450–459, 2003[Abstract/Free Full Text]
  • Currie RW. Effect of ischemia and perfusion temperature on the synthesis of stress-induced (heat-shock) proteins in isolated and perfused rat hearts. J Mol Cell Cardiol 19:795–808, 1987[ISI][Medline] [Order article via Infotrieve]
  • Currie RW, Karmazyn M, Kloc M, et al. Heat shock response is associated with enhanced postischemic ventricular recovery. Circ Res 63:543–549, 1988[Abstract/Free Full Text]
  • Marber MS, Mestrl R, Chi SH, et al. Overexpression of the rat inducible 70 kDa heat shock protein in a transgenic mouse increases the resistance of the heart to ischemic injury. J Clin Invest 95:1446–1456, 1995[ISI][Medline] [Order article via Infotrieve]
  • Okubo S, Wildner O, Shah MR, et al. Gene transfer of heat-shock protein 70 reduces infarct size in vivo after ischemia/reperfusion in rabbit heart. Circulation 103:877–881, 2001[Abstract/Free Full Text]
  • Das DK, Maulik N, Moratu II. Gene expression in acute myocardial stress. Induction by hypoxia, ischemia, reper-fusion, hyperthermia and oxidative stress. J Mol Cell Cardiol 27:181–193, 1995[ISI][Medline] [Order article via Infotrieve]
  • Hsu JC, Bravo R, Taub R. Interaction among LRF-1, JunB, c-Jun, and c-Fos define a regulatory program in the G1 phase of liver regeneration. Mol Cell Biol 12:4654–4665, 1992[Abstract/Free Full Text]
  • Nobori K, Ito H, Tamamori-Adachi M, et al. ATF3 inhibits doxorubicin-induced apoptosis in cardiac myocytes: A novel cardioprotective role of ATF3. J Mol Cell Cardiol 34:1387–1397, 2002[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Kwaan HC, Wang J, Svoboda K, et al. Plasminogen activator inhibitor 1 may promote tumour growth through inhibition of apoptosis. Br J Cancer 82:1702–1709, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Soeda S, Oda M, Ochiai T, et al. Deficient release of plasminogen activator inhibitor-1 from astrocytes triggers apoptosis in neuronal cells. Brain Res 91:96–103, 2001
  • Corrente G, Guardavaccaro D, Tirone F. PC3 potentiates NGF-induced differentiation and protects neurons from apoptosis. Neuroreport 13:417–422, 2002[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Hollander MC, Sheikh MS, Bulavin DV, et al. Genomic instability in Gadd45a-deficient mice. Nat Genet 23:176–184, 1999[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Pislaru SV, Simari RD. Gene transfer for ischemic cardiovascular disease: Is this the end of the beginning or the beginning of the end? Nat Clin Pract Cardiovasc Med 2:138–144, 2005[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Dishart KL, Work LM, Denby L, et al. Gene therapy for cardiovascular disease. J Biomed Biotechnol 2003:138–148, 2003[CrossRef][Medline] [Order article via Infotrieve]
  • Symes JF. Gene therapy for ischemic heart disease: Therapeutic potential. Am J Cardiovasc Drugs 1:159–166, 2001[CrossRef][Medline] [Order article via Infotrieve]
  • Losordo DW, Vale PR, Symes JF, et al. Gene therapy for myocardial angiogenesis: Initial clinical results with direct myocardial injection of phVEGF165 as sole therapy for myocardial ischemia. Circulation 98:2800–2804, 1998[Abstract/Free Full Text]
  • Rosengart TK, Lee LY, Patel SR, et al. Angiogenesis gene therapy: Phase I assessment of direct intramyocardial administration of an adenovirus vector expressing VEGF121 cDNA to individuals with clinically significant severe coronary artery disease. Circulation 100:468–474, 1999[Abstract/Free Full Text]
  • Symes JF, Losordo DW, Vale PR, et al. Gene therapy with vascular endothelial growth factor for inoperable coronary artery disease. Ann Thor Surg 68:830–837, 1999[Abstract/Free Full Text]
  • Vale PR, Losordo DW, Milliken CE, et al. Left ventricular electromechanical mapping to assess efficacy of phVEGF165 gene transfer for therapeutic angiogenesis in chronic myocardial ischemia. Circulation 102:965–974, 2000[Abstract/Free Full Text]
  • Fortuin Jr FD, Vale P, Losordo DW, et al. One-year follow-up of direct myocardial gene transfer of vascular endothelial growth factor-2 using naked plasmid DNA by way of thoracotomy in no-option patients. Am J Cardiol 92:436–439, 2003[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Sarkar N, Ruck A, Kallner G, et al. Effects of intramyocardial injection of phVEGF-A165 as sole therapy in patients with refractory coronary artery disease—12-month follow-up: Angiogenic gene therapy. J Intern Med 250:373–381, 2001[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Vale PR, Losordo DW, Milliken CE, et al. Randomized, single-blind, placebo-controlled pilot study of catheter-based myocardial gene transfer for therapeutic angiogenesis using left ventricular electromechanical mapping in patients with chronic myocardial ischemia. Circulation 103:2138–2143, 2001[Abstract/Free Full Text]
  • Losordo DW, Vale PR, Hendel RC, et al. Phase 1/2 placebo-controlled, double-blind, dose-escalating trial of myocardial vascular endothelial growth factor 2 gene transfer by catheter delivery in patients with chronic myocardial ischemia. Circulation 105:2012–2018, 2002[Abstract/Free Full Text]
  • Hedman M, Hartikainen J, Syvanne M, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia: Phase II results of the Kuopio Angiogenesis Trial (KAT). Circulation 107:2677–2683, 2003[Abstract/Free Full Text]
  • Kastrup J, Jorgensen E, Ruck A, et al. Direct intramyocar-dial plasmid vascular endothelial growth factor-A165 gene therapy in patients with stable severe angina pectoris. A randomized double-blind placebo-controlled study: The Euroinject One Trial. J Am Coll Cardiol 45:982–988, 2005[Abstract/Free Full Text]
  • Schuh A, Breuer S, Dashti RA, et al. Administration of vascular endothelial growth factor adjunctive to fetal cardiomyocyte transplantation and improvement of cardiac function in the rat model. J Cardiovasc Pharmacol Therapeut 10:55–66, 2005[Abstract/Free Full Text]
  • Henry TD, Annex BH, McKendall GR, et al. The VIVA trial: Vascular endothelial growth factor in ischemia for vascular angiogenesis. Circulation 107:1359–1365, 2003[Abstract/Free Full Text]
  • Laham RJ, Chronos NA, Pike M, et al. Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: Results of a phase I open-label dose escalation study. J Am Coll Cardiol 36:2132–2139, 2000[Abstract/Free Full Text]
  • Unger EF, Goncalves L, Epstein SE, et al. Effects of a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris. Am J Cardiol 85:1414–1419, 2000[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Simons M, Annex BH, Laham RJ, et al. Pharmacological treatment of coronary artery disease with recombinant fibroblast growth factor-2: Double-blind, randomized, controlled clinical trial. Circulation 105:788–793, 2002[Abstract/Free Full Text]
  • Grines CL, Watkins MW, Helmer G, et al. Angiogenic gene therapy (AGENT) trial in patients with stable angina. Circulation 105:1291–1297, 2002[Abstract/Free Full Text]
  • Grines CL, Watkins MW, Mahmarian JJ, et al. A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina. J Am Coll Cardiol 42:1339–1347, 2003[Abstract/Free Full Text]
  • Grines, CL. The AGENT clinical trials programme. Eur Heart J Supp 6 suppl E:18–23, 2004[CrossRef]
  • Li Q, Bolli R, Qiu Y, et al. Gene therapy with extracellular superoxide dismutase attenuates myocardial stunning in conscious rabbits. Circulation 98:1438–1448, 1998[Abstract/Free Full Text]
  • Karlsson K, Marklund SL. Heparin-, dextran sulfate-, and protamine-induced release of extracellular-superoxide dismutase to plasma in pigs. Biochim Biophys Acta 967:110–114, 1988[Medline] [Order article via Infotrieve]
  • Li Q, Bolli R, Qiu Y, et al. Gene therapy with extracellular superoxide dismutase protects conscious rabbits against myocardial infarction. Circulation 103:1893–1898, 2001[Abstract/Free Full Text]
  • Melo LG, Agrawal R, Zhang L, et al. Gene therapy strategy for long-term myocardial protection using adeno-associated virus-mediated delivery of heme oxygenase gene. Circulation 105:602–607, 2002[Abstract/Free Full Text]
  • Melo LG, Zhang L, Pachori AS, et al. Preemptive gene therapy by AAV-mediated delivery of heme oxygenase-1 results in long-term normalization of left ventricular function and chamber dimensions. Circulation 108 (suppl IV):IV-144, 2003
  • Platt JL, Nath KA. Heme oxygenase: Protective gene or Trojan horse. Nat Med 4:1364–1365, 1998[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Phillips MI, Tang Y, Schmidt-Ott K, et al. Vigilant vector: Heart-specific promoter in an adeno-associated virus vec tor for cardioprotection. Hypertension 39:651–655, 2002[Abstract/Free Full Text]
  • Tang YL, Tang Y, Zhang YC, et al. Protection from ischemic heart injury by a vigilant heme oxygenase-1 plas mid system. Hypertension 43:746–751, 2004[Abstract/Free Full Text]
  • Pachori AS, Melo LG, Hart ML, et al. Hypoxia-regulated therapeutic gene as a preemptive treatment strategy against ischemia/reperfusion injury. Proc Natl Acad Sci 101:12282–12287, 2004[Abstract/Free Full Text]
  • Sesti C, Kloner RA. Gene therapy in congestive heart failure. Circulation 110:242–243, 2004[Free Full Text]
  • Lefkowitz RJ, Rockman HA, Koch WJ. Catecholamines, cardiac beta-adrenergic receptors, and heart failure. Circulation 101:1634–1637, 2000[Free Full Text]
  • Rockman HA, Koch WJ, Lefkowitz RJ. Seven-transmem brane-spanning receptors and heart function. Nature 415:206–212, 2002[CrossRef][Medline] [Order article via Infotrieve]
  • Petrofski JA, Koch WJ. The b-adrenergic receptor kinase in heart failure. J Mol Cell Cardiol 35:1167–1174, 2003[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ungerer M, Bohm M, Elce JS, et al. Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart. Circulation 87:454–463, 1993[Abstract/Free Full Text]
  • Harding VB, Jones LR, Lefkowitz RJ, et al. Cardiac beta ARK1 inhibition prolongs survival and augments beta blocker therapy in a mouse model of severe heart failure. Proc Natl Acad Sci USA 98:5809–5814, 2001[Abstract/Free Full Text]
  • Manning BS, Shotwell K, Mao L, et al. Physiological induction of a beta-adrenergic receptor kinase inhibitor transgene preserves ss-adrenergic responsiveness in pressure-overload cardiac hypertrophy. Circulation 102:2751–2757, 2000[Abstract/Free Full Text]
  • Shah AS, White DC, Emani S, et al. In vivo ventricular gene delivery of a beta-adrenergic receptor kinase inhibitor to the failing heart reverses cardiac dysfunction. Circulation 103:1311–1316, 2001[Abstract/Free Full Text]
  • White DC, Hata JA, Shah AS, et al. Preservation of myocardial beta-adrenergic receptor signaling delays the development of heart failure after myocardial infarction. Proc Natl Acad Sci USA 97:5428–5433, 2000[Abstract/Free Full Text]
  • Akhter SA, Eckhart AD, Rockman HA, et al. In vivo inhibition of elevated myocardial beta-adrenergic receptor kinase activity in hybrid transgenic mice restores normal beta-adrenergic signaling and function. Circulation 100:648–653, 1999[Abstract/Free Full Text]
  • Rockman HA, Chien KR, Choi DJ, et al. Expression of beta-adrenergic receptor kinase 1 inhibitor prevents the development of myocardial failure in gene-targeted mice. Proc Natl Acad Sci USA 95:7000–7005, 1998[Abstract/Free Full Text]
  • Suzuki Y, Nakano K, Sugiyama M, et al. bARK1 inhibition improves survival in a mouse model of heart failure induced by myocardial infarction. J Cardiovasc Pharmacol 44:329–334, 2004[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Williams ML, Hata JA, Schroder J, et al. Targeted b-adrenergic receptor kinase (bARK1) inhibition by gene transfer in failing human hearts. Circulation 109:1590–1593, 2004[Abstract/Free Full Text]
  • Lai NC, Roth DM, Gao MH, et al. Intracoronary aden-ovirus encoding adenylyl cyclase VI increases left ventricular function in heart failure. Circulation 110:330–336, 2004[Abstract/Free Full Text]
  • Miyamoto MI, del Monte F, Schmidt U, et al. Adenoviral gene transfer of SERCA2a improves left-ventricular function in aortic-banded rats in transition to heart failure. Proc Natl Acad Sci USA 97:793–798, 2000[Abstract/Free Full Text]
  • del Monte F, Williams E, Lebeche D, et al. Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca2+-ATPase in a rat model of heart failure. Circulation 104:1424–1429, 2001[Abstract/Free Full Text]
  • Remppis A, Greten T, Schafer BW, et al. Altered expression of the Ca2+-binding protein S100A1 in human cardiomyopathy. Biochim Biophys Acta 1313:253–257, 1996[Medline] [Order article via Infotrieve]
  • Most P, Pleger ST, Völkers M, et al. Cardiac adenoviral S100A1 gene delivery rescues failing myocardium. J Clin Invest 114:1550–1563, 2004[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Iwanaga Y, Hoshijima M, Gu Y, et al. Chronic phospholamban inhibition prevents progressive cardiac dysfunction and pathological remodeling after infarction in rats. J Clin Invest 113:727–736, 2004[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Ziolo MT, Martin JL, Bossuyt J, et al. Adenoviral genetransfer of mutant phospholamban rescues contractile dysfunction in failing rabbit myocytes with relatively preserved SERCA function. Circ Res 96:815–817, 2005[Abstract/Free Full Text]
  • del Monte F, Harding SE, Dec GW, et al. Targeting phospholamban by gene transfer in human heart failure. Circulation 105:904–907, 2002[Abstract/Free Full Text]
  • Kirshenbaum LA, de Moissac D. The bcl-2 gene product prevents programmed cell death of ventricular myocytes. Circulation 96:1580–1585, 1997[Abstract/Free Full Text]
  • Matsui T, Li L, del Monte F, et al. Adenoviral gene transfer of activated phosphatidylinositol 3’-kinase and Akt inhibits apoptosis of hypoxic cardiomyocytes in vitro. Circulation 100:2373–2379, 1999[Abstract/Free Full Text]
  • Fujio Y, Nguyen T, Wencker D, et al. Akt promotes survival of cardiomyocytes in vitro and protects against ischemia-reperfusion injury in mouse heart. Circulation 101:660–667, 2000[Abstract/Free Full Text]
  • Cheng JC, Moore TB, Sakamoto KM. RNA interference and human disease. Mol Genet Metab 80:121–128, 2003[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Morris KV, Chan SW, Jacobsen SE, et al. Small interfering RNA-induced transcriptional gene silencing in human cells. Science 305:1289–1292, 2004[Abstract/Free Full Text]
  • Kawasaki H, Taira K. Induction of DNA methylation and gene silencing by short interfering RNAs in human cells. Nature 431:211–217, 2004[CrossRef][Medline] [Order article via Infotrieve]
  • Robb GB, Brown KM, Khurana J, et al. Specific and potent RNAi in the nucleus of human cells. Nat Struct Mol Biol 12:133–137, 2005[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Yague E, Higgins CF, Raguz S. Complete reversal of multidrug resistance by stable expression of small interfering RNAs targeting MDR1. Gene Ther 11:1170–1174, 2004[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • McCaffrey AP, Meuse L, Pham TT, et al. RNA interference in adult mice. Nature 418:38–39, 2002[CrossRef][Medline] [Order article via Infotrieve]
  • Hamilton AJ, Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286:950–952, 1999[Abstract/Free Full Text]
  • Ishizuka A, Siomi MC, Siomi H. A Drosophila fragile X protein interacts with components of RNAi and ribosomal proteins. Genes Dev 16:2497–2508, 2002[Abstract/Free Full Text]
  • Calin GA, Dumitru CD, Shimizu M, et al. Frequent deletions and down-regulation of micro-RNA genes miR15 and miR16 at 13q14 in chronic lymphocytic leukemia. Proc Natl Acad Sci USA 99:15524–15529, 2002[Abstract/Free Full Text]
  • Jin P, Alisch RS, Warren ST. RNA and microRNAs in fragile X mental retardation. Nat Cell Biol 6:1048–1053, 2004[CrossRef][ISI][Medline] [Order article via Infotrieve]
  • Soutschek J, Akinc A, Bramlage B, et al. Therapeutic silencing of an endogenous gene by systemic administration of modified siRNAs. Nature 432:173–178, 2004[CrossRef][Medline] [Order article via Infotrieve]
  • Tang YL, Tang Y, Zhang YC, et al. Improved graft mesenchymal stem cell survival in ischemic heart with a hypoxia-regulated heme oxygenase-1 vector. J Am Coll Cardiol 46:1339–1350, 2005[Abstract/Free Full Text]
  • Dzau VJ, Gnecchi M, Pachori AS. Enhancing stem cell therapy through genetic modification. J Am Coll Cardiol 46:1351–1353, 2005[Free Full Text]
  • Gnecchi M, He H, Liang OD. Paracrine action accounts for marked protection of ischemic heart by Akt-modified mesenchymal stem cells. Nat Med 11:367–368, 2005[CrossRef][ISI][Medline] [Order article via Infotrieve]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
Brief BioinformHome page
B. C. Thorne, A. M. Bailey, and S. M. Peirce
Combining experiments with multi-cell agent-based modeling to study biological tissue patterning
Brief Bioinform, July 1, 2007; 8(4): 245 - 257.
[Abstract] [Full Text] [PDF]


Home page
Am. J. Physiol. Heart Circ. Physiol.Home page
J.-X. Chen, H. Zeng, Q.-H. Tuo, H. Yu, B. Meyrick, and J. L. Aschner
NADPH oxidase modulates myocardial Akt, ERK1/2 activation, and angiogenesis after hypoxia-reoxygenation
Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1664 - H1674.
[Abstract] [Full Text] [PDF]


This Article
Right arrow Abstract Freely available
Right arrow Free Full Text (Free PDF) Free
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to Saved Citations
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Request Reprints
Right arrow Add to My Marked Citations
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nordlie, M. A.
Right arrow Articles by Kloner, R. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nordlie, M. A.
Right arrow Articles by Kloner, R. A.
Social Bookmarking
 Add to CiteULike   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?