Novel Therapeutic Targets in Myocardial Infarction
Posted March 01, 2013
Every year, millions of people develop myocardial infarctions, commonly known as heart attacks, in which a loss of blood flow causes a portion of the heart muscle to die. Current treatments can save upwards of 80% of these patients, but the underlying condition that causes infarction, ischemic heart disease, often leads to chronic, life-shortening problems. According to the World Health Organization, ischemic heart disease accounts for about 12% of deaths worldwide.
On December 14, 2012, the New York Academy of Sciences presented Novel Therapeutic Targets in Myocardial Infarction, a Hot Topics in Life Sciences symposium which highlighted new strategies and technologies, as well as the significant challenges this condition presents. Speakers discussed new treatments, like cellular repair through bone marrow-derived mononuclear cells and efferocytosis; new findings on the dual role of inflammatory processes; avenues opened through nanotechnology; insights from genome analysis; and novel techniques for measuring endothelial damage. The symposium also delved into one of the field's toughest challenges, predicting heart attacks, and looked at the events following an infarction, when the heart repairs and remodels injured tissue. Though much of this research highlights the deep complexity of ischemic heart disease, it also reveals new treatment possibilities.
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Presentations available from:
Paddy Barrett, MD (Scripps Translational Science Institute)
Buddhadeb Dawn, MD (University of Kansas Medical Center)
Zahi A. Fayad, PhD (Mount Sinai School of Medicine)
Barbara Hempstead, MD, PhD (Weill Cornell Medical College)
Elizabeth McNally, MD, PhD (The University of Chicago Medicine)
Filip Swirski, PhD (Massachusetts General Hospital; Harvard Medical School)
Edward Thorp, PhD (Northwestern University)
Barrett PM, Topol EJ. The fibrillin-1 gene: Unlocking new therapeutic pathways in cardiovascular disease. Heart. 2013;99(2):83-90. [Epub 2012]
Barrett PM, Topol EJ. Pharmacogenetics: Point-of-care genetic testing — a new frontier explored. Nat Rev Cardiol. 2012;9(6):315-6.
Barrett PM, Alagely A, Topol EJ. Cystic fibrosis in an era of genomically guided therapy. Hum Mol Genet. 2012;21(R1):R66-71. [Epub 2012]
Dawn B, Abdel-Latif A, Sanganalmath SK, Flaherty MP, Zuba-Surma EK. Cardiac repair with adult bone marrow-derived cells: the clinical evidence. Antioxid Redox Signal. 2009;11(8):1865-82.
Jeevanantham V, Butler M, Saad A, Abdel-Latif A, Zuba-Surma EK, Dawn B. Adult bone marrow cell therapy improves survival and induces long-term improvement in cardiac parameters: a systematic review and meta-analysis. Circulation. 2012;126(5):551-68. [Epub 2012]
Sanganalmath SK, Abdel-Latif A, Bolli R, Xuan YT, Dawn B. Hematopoietic cytokines for cardiac repair: mobilization of bone marrow cells and beyond. Basic Res Cardiol. 2011;106(5):709-33. [Epub 2011]
Zahi A. Fayad
Bini J, Izquierdo-Garcia D, Mateo J, et. al. Preclinical evaluation of MR attenuation correction versus CT attenuation correction on a sequential whole-body MR/PET scanner. Invest Radiol. 2013. [Epub ahead of print]
Hyafil F, Feldman L, Le Guludec D, Fayad ZA. Evaluating efficacy of pharmaceutical interventions in atherosclerosis: role of magnetic resonance imaging and positron emission tomography. Mt Sinai J Med. 2012;79(6):689-704.
Rosenbaum D, Millon A, Fayad ZA. Molecular imaging in atherosclerosis: FDG PET. Curr Atheroscler Rep. 2012;14(5):429-37.
Deinhardt K, Kim T, Spellman DS, et. al. Neuronal growth cone retraction relies on proneurotrophin receptor signaling through Rac. Sci Signal. 2011;4(202):ra82.
Siao CJ, Lorentz CU, Kermani P, et. al. ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation. J Exp Med. 2012;209(12):2291-305. [Epub 2012]
Song W, Volosin M, Cragnolini AB, Hempstead BL, Friedman WJ. ProNGF induces PTEN via p75NTR to suppress Trk-mediated survival signaling in brain neurons. J Neurosci. 2010;30(46):15608-15.
Das D, Gawdzik J, Dellefave-Castillo L, et. al. S100A12 expression in thoracic aortic aneurysm is associated with increased risk of dissection and perioperative complications. J Am Coll Cardiol. 2012;60(8):775-85. [Epub 2012]
Golbus JR, Puckelwartz MJ, Fahrenbach JP, Dellefave-Castillo LM, Wolfgeher D, McNally EM. Population-based variation in cardiomyopathy genes. Circ Cardiovasc Genet. 2012;5(4):391-9. [Epub 2012]
McNally EM, Golbus JR, Puckelwartz MJ. Genetic mutations and mechanisms in dilated cardiomyopathy. J Clin Invest. 2013;123(1):19-26. [Epub 2013]
Dutta P, Courties G, Wei Y, et. al. Myocardial infarction accelerates atherosclerosis. Nature. 2012;487(7407):325-9.
Robbins CS, Chudnovskiy A, Rauch PJ, Figueiredo JL, et. al. Extramedullary hematopoiesis generates Ly-6C(high) monocytes that infiltrate atherosclerotic lesions. Circulation. 2012;125(2):364-74. [Epub 2011]
Swirski FK, Nahrendorf M. Leukocyte behavior in atherosclerosis, myocardial infarction, and heart failure. Science. 2013;339(6116):161-6.
Thorp E, Iwawaki T, Miura M, Tabas I. A reporter for tracking the UPR in vivo reveals patterns of temporal and cellular stress during atherosclerotic progression. J Lipid Res. 2011;52(5):1033-8. [Epub 2011]
Thorp E, Subramanian M, Tabas I. The role of macrophages and dendritic cells in the clearance of apoptotic cells in advanced atherosclerosis. Eur J Immunol. 2011;41(9):2515-8.
Thorp E, Vaisar T, Subramanian M, Mautner L, Blobel C, Tabas I. Shedding of the Mer tyrosine kinase receptor is mediated by ADAM17 protein through a pathway involving reactive oxygen species, protein kinase C-delta, and p38 mitogen-activated protein kinase (MAPK). J Biol Chem. 2011;286(38):33335-44.
Mercedes Beyna, MS
Mercedes Beyna is a research scientist at Pfizer, where she is using molecular, cellular, genetic, and imaging approaches in the quest to understand the biology underlying autism spectrum disorders. Captivated by neuroscience, she has worked in the field for over 10 years, in both academic and industrial laboratory settings. Beyna attended Binghamton University, earning her undergraduate degree in biology, and subsequently received her master's degree in Biology from New York University. As an active member of the Biochemical Pharmacology Discussion Group, she enjoys developing interesting and educational symposia.
Mark Kaplan, PhD
Mark Kaplan is a senior principal scientist at Pfizer's Centers for Therapeutic Innovation (CTI). He obtained his PhD in biophysics at the University of California, San Francisco, and was a Leukemia Society postdoctoral fellow in genetics at the University of Wisconsin. Kaplan transitioned into industry and has worked as a scientist at Deltagen, Exelixis, Celera Genomics, and Roche, focusing on both oncology and RNAi. He recently joined Pfizer's CTI New York and is leading collaboration with Weill Cornell Medical College to develop a monoclonal antibody to mitigate cardiac remodeling following an acute myocardial infarction.
Laurent Yvan-Charvet, PhD
Laurent Yvan-Charvet is a lab head in the CVMED research unit at Pfizer, Inc. He obtained his PhD in endocrinology from the University of Paris XI, France, and completed postdoctoral cardiovascular training at Columbia University on the role of cholesterol efflux pathways in inflammation and stem cell biology. He joined Pfizer in 2012 and hopes to contribute to the development of new therapeutics for cardiovascular diseases. Yvan-Charvet received the Roger Davis Award in 2010.
Jennifer Henry, PhD
The New York Academy of Sciences
Jennifer Henry is the director of Life Sciences at the New York Academy of Sciences. Henry joined the Academy in 2009, before which she was a publishing manager in the Academic Journals division at Nature Publishing Group. She also has eight years of direct editorial experience as editor of Functional Plant Biology for CSIRO Publishing in Australia. She received her PhD in plant molecular biology from the University of Melbourne, specializing in the genetic engineering of transgenic crops. As director of Life Sciences, she is responsible for developing scientific symposia across a range of life sciences, including biochemical pharmacology, neuroscience, systems biology, genome integrity, infectious diseases and microbiology. She also generates alliances with organizations interested in developing programmatic content.
Paddy Barrett, MD
Paddy Barrett graduated from University College Dublin, Ireland, and completed residency training in major tertiary centers in Sydney, Australia, and Dublin, Ireland. His research focuses on personalized medicine and wireless health technologies, particularly the molecular and genomic characterization of circulating endothelial cells released during myocardial infarction. He is interested in how technology can revolutionize tailored diagnostics and therapeutics. He is the winner of the A. Menarini/Irish Cardiac Society Travelling Research Scholarship and the McArdle Prize in surgery for outstanding academic performance and is a member of the Royal College of Physicians of Ireland.
Buddhadeb Dawn, MD
Buddhadeb Dawn is the Maureen and Marvin Dunn Professor and director of the Division of Cardiovascular Diseases at the University of Kansas Medical Center. He is also the vice chair for research in the Department of Medicine and director of the Cardiovascular Research Institute at KU. A graduate of Calcutta Medical College, Dawn completed his residency at the University of Missouri–Columbia and a cardiology fellowship at the University of Louisville. His research focuses on heart repair by adult stem cells and his clinical interests include echocardiography and atrial fibrillation. Dawn is a fellow of the American Heart Association and the American College of Cardiology and serves on grant review panels and the editorial boards of several leading cardiovascular journals.
Zahi A. Fayad, PhD
Zahi A. Fayad attended Johns Hopkins University and the University of Pennsylvania and was a junior faculty member in the Department of Radiology at the University of Pennsylvania before joining Mount Sinai School of Medicine, where he is a professor of radiology and medicine (cardiology). He is the director of the Translational and Molecular Imaging Institute and vice chair for research in the Department of Radiology. His interdisciplinary and broad-scope research—from engineering to biology and from pre-clinical to clinical investigations—has been dedicated to detecting and preventing cardiovascular disease, with a focus on biomedical imaging.
Barbara Hempstead, MD, PhD
Barbara Hempstead is a professor of medicine and associate dean for faculty development at Weill Cornell Medical College. She obtained her MD/PhD training at Washington University in St. Louis, followed by clinical training in internal medicine and hematology and medical oncology at New York Hospital–Cornell Medical Center. She has studied the biological actions of neurotrophins for more than 20 years. She was a member of the team that initially identified Trk as the survival-promoting NGF receptor and more recently identified proneurotrophins as distinct signaling molecules that selectively bind p75 to induce cell death. Her laboratory has described important roles for these molecules in the nervous system and the vasculature.
Elizabeth McNally, MD, PhD
Elizabeth McNally is a professor in the Department of Medicine and the Department of Human Genetics at the University of Chicago. McNally directs the Institute for Cardiovascular Research and the Cardiovascular Genetics Clinic at the University of Chicago. She earned her MD and PhD degrees at Albert Einstein College of Medicine and completed training in internal medicine and cardiovascular medicine at Brigham and Women's Hospital and at Harvard Medical School. McNally is principal investigator on NIH grants to discern genetic disease mechanisms in heart and muscle disease. Her special clinical interests are in treating patients with inherited forms of cardiovascular disease including cardiomyopathy, cardiovascular complications of neuromuscular disease, and inherited aortic vascular disease.
Sharon Sokolowski, PhD
Sharon Sokolowski is a senior principal scientist in Drug Safety Research and Development at Pfizer and leads the Biomarkers Flow Cytometry lab in Groton, Connecticut. She has held multiple positions at Pfizer ranging from bench scientist to laboratory manager, and after spending several years in infectious disease and immunology is now focused on drug safety. The Biomarker Flow Cytometry lab supports biomarker development, regulatory toxicity studies, and mechanistic investigations.
Filip Swirski, PhD
Filip Swirski is an assistant professor at Harvard Medical School and Massachusetts General Hospital. Swirski obtained his PhD in immunology from McMaster University in Canada and completed his postdoctoral studies in vascular biology at Brigham and Women's Hospital and Massachusetts General Hospital. His lab focuses on leukocytedynamics in cardiovascular disease. He is currently working on how extramedullary myelopoiesis influences the evolution of atherosclerotic lesions.
Edward Thorp, PhD
Edward Thorp received his PhD in microbiology and immunology from Loyola University Chicago for work on virus infection and assembly in cholesterol-rich membrane micro-domains. His interest in cholesterol led to studies of atherosclerosis as an American Heart Association postdoctoral fellow in the Department of Medicine at Columbia University. During this time, he focused on the unfolded protein stress response and the resolution of inflammation by macrophages. Thorp is now an assistant professor in the Department of Pathology and an associate of the Feinberg Cardiovascular Research Institute in the Feinberg School of Medicine at Northwestern University. His current research focuses on myocardial cell stress and inflammation-resolution post myocardial infarction.
Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism and blogs at http://dovdox.com.