Roberto Bolli, MD
Director, Institure of Molecular Cardiology
Chief, Division of Cardiology
Vice Chairmen for Research, Department of Medicine
Professor of Medicine, Physiology & Biophysics
Distinguished University Scholar
Jewish Hospital Heart & Lung Institure
Distinguished Chair in Cardiology
Dr. Bolli’s research involves the mechanism of the late phase of ischemic preconditioning (PC). Late PC is the phenomenon whereby exposure of the heart to a brief ischemic stress induces a delayed, relatively sustained protective response against subsequent ischemic injury, which is fully manifest 24-72 h later. Because late PC is long lasting and results in a powerful protection against both myocardial infarction and myocardial dysfunction (i.e., stunning), it has great potential clinical implications. Using a conscious rabbit model of late PC, Dr. Bolli has shown that oxyradicals are involved in late PC, and that nitric oxide synthase (NOS) and its product nitric oxide (NO) play key roles in the mechanism of late PC. Specifically, Dr. Bolli has demonstrated that NO produced from a constitutive NOS (probably eNOS) acts as the trigger for late PC on day 1, while NO produced from iNOS acts as the mediator of late PC on day 2. More recently, using an open-chest mouse model of late PC and mice bearing gene targeted ablations of iNOS, Dr. Bolli has shown that iNOS plays an obligatory role in late PC and that NO-donors are able to induce late PC against both myocardial stunning and infarction. Ongoing research includes clinical studies of NO-donors to induce late PC in patients with coronary artery disease, and collaborative studies with molecular biologists in the Division to elucidate the cellular and molecular mechanisms that underlie the late phase of ischemic PC. The long-range goals of Dr. Bolli’s research are to elucidate the cellular mechanism of late PC, and to use this knowledge to reproduce this cardioprotective phenomenon in the clinical setting via pharmacologic and/or gene therapeutic means.
Selected Recent Publications:
- Chugh AR, Beache GM, Loughran JH, Mewton N, Elmore JB, Kajstura J, Pappas P, Tatooles A, Stoddard MF, Lima JA, Slaughter MS, Anversa P, Bolli R., Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation. 2012 Sep 11;126(11 Suppl 1):S54-64.
- Guo Y, Flaherty MP, Wu WJ, Tan W, Zhu X, Li Q, Bolli R. Genetic background, gender, age, body temperature, and arterial blood pH have a major impact on myocardial infarct size in the mouse and need to be carefully measured and/or taken into account: results of a comprehensive analysis of determinants of infarct size in 1,074 mice. Basic Res Cardiol. 2012 Sep;107(5):288. doi: 10.1007/s00395-012-0288-y. Epub 2012 Aug 3.
- Bolli R, Chugh AR, D'Amario D, Loughran JH, Stoddard MF, Ikram S, Beache GM, Wagner SG, Leri A, Hosoda T, Sanada F, Elmore JB, Goichberg P, Cappetta D, Solankhi NK, Fahsah I, Rokosh DG, Slaughter MS, Kajstura J, Anversa P. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet. 2011 Nov 26;378(9806):1847-57. Epub 2011 Nov 14.
- Li Q, Guo Y, Ou Q, Wu WJ, Chen N, Zhu X, Tan W, Yuan F, Dawn B, Luo L, Hunt GN, Bolli R. Gene transfer as a strategy to achieve permanent cardioprotection II: rAAV-mediated gene therapy with heme oxygenase-1 limits infarct size 1 year later without adverse functional consequences. Basic Res Cardiol. 2011 Nov;106(6):1367-77. doi: 10.1007/s00395-011-0208-6. Epub 2011 Jul 22.
- Tang XL, Rokosh G, Sanganalmath SK, Yuan F, Sato H, Mu J, Dai S, Li C, Chen N, Peng Y, Dawn B, Hunt G, Leri A, Kajstura J, Tiwari S, Shirk G, Anversa P, Bolli R. Intracoronary administration of cardiac progenitor cells alleviates left ventricular dysfunction in rats with a 30-day-old infarction. Circulation. 2010 Jan 19;121(2):293-305. Epub 2010 Jan 4.
- Dawn B, Tiwari S, Kucia MJ, Zuba-Surma EK, Guo Y, Sanganalmath SK, Abdel-Latif A, Hunt G, Vincent RJ, Taher H, Reed NJ, Ratajczak MZ, Bolli R. Transplantation of bone marrow-derived very small embryonic-like stem cells attenuates left ventricular dysfunction and remodeling after myocardial infarction. Stem Cells. 2008 Jun;26(6):1646-55. doi: 10.1634/stemcells.2007-0715. Epub 2008 Apr 17.
- Li Q, Guo Y, Ou Q, Cui C, Wu WJ, Tan W, Zhu X, Lanceta LB, Sanganalmath SK, Dawn B, Shinmura K, Rokosh GD, Wang S, Bolli R. Gene transfer of inducible nitric oxide synthase affords cardioprotection by upregulating heme oxygenase-1 via a nuclear factor-{kappa}B-dependent pathway. Circulation. 2009 Sep 29;120(13):1222-30. doi: 10.1161/CIRCULATIONAHA.108.778688. Epub 2009 Sep 14.
- Li Q, Guo Y, Tan W, Ou Q, Wu WJ, Sturza D, Dawn B, Hunt G, Cui C, Bolli R. Cardioprotection afforded by inducible nitric oxide synthase gene therapy is mediated by cyclooxygenase-2 via a nuclear factor-kappaB dependent pathway. Circulation. 2007 Oct 2;116(14):1577-84. Epub 2007 Sep 4.
- Dawn B, Guo Y, Rezazadeh A, Huang Y, Stein AB, Hunt G, Tiwari S, Varma J, Gu Y, Prabhu SD, Kajstura J, Anversa P, Ildstad ST, Bolli R. Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function. Circ Res. 2006 Apr 28;98(8):1098-105. Epub 2006 Mar 23.
- Xuan YT, Guo Y, Zhu Y, Wang OL, Rokosh G, Bolli R. Endothelial nitric oxide synthase plays an obligatory role in the late phase of ischemic preconditioning by activating the protein kinase C epsilon p44/42 mitogen-activated protein kinase pSer-signal transducers and activators of transcription1/3 pathway. Circulation. 2007 Jul 31;116(5):535-44. Epub 2007 Jul 2.
- Jneid H, Chandra M, Alshaher M, Hornung CA, Tang XL, Leesar M, Bolli R. Delayed preconditioning-mimetic actions of nitroglycerin in patients undergoing exercise tolerance tests. Circulation. 2005 May 24;111(20):2565-71. Epub 2005 May 16.
- Dawn B, Guo Y, Rezazadeh A, Huang Y, Stein AB, Hunt G, Tiwari S, Varma J, Gu Y, Prabhu SD, Kajstura J, Anversa P, Ildstad ST, Bolli R. Postinfarct cytokine therapy regenerates cardiac tissue and improves left ventricular function. Circ Res. . 2006 Apr 28;98(8):1098-105. Epub 2006 Mar 23.
- Dawn B, Stein AB, Urbanek K, Rota M, Whang B, Rastaldo R, Torella D, Tang XL, Rezazadeh A, Kajstura J, Leri A, Hunt G, Varma J, Prabhu SD, Anversa P, Bolli R. Cardiac stem cells delivered intravascularly traverse the vessel barrier, regenerate infarcted myocardium, and improve cardiac function. Proc Natl Acad Sci U S A. 2005 Mar 8;102(10):3766-71. Epub 2005 Feb 25.
- Bolli R. The new circulation research: a manifesto. Circ Res. 2010 Feb 5;106(2):216-26.
- Li Q, Guo Y, Xuan YT, Lowenstein CJ, Stevenson SC, Prabhu SD, Wu WJ, Zhu Y, Bolli R. Gene therapy with inducible nitric oxide synthase protects against myocardial infarction via a cyclooxygenase-2-dependent mechanism. Circ Res. 2003 Apr 18;92(7):741-8.
