19. Profibrotic and Angiogenic Factors in Asthma

  1. Kenji Izuhara MD, PhD3,
  2. Stephen T. Holgate MD, DSc, FMedSci4 and
  3. Marsha Wills-Karp PhD5
  1. Neville Berkman MBBCh, FRCP1 and
  2. Francesca Levi-Schaffer PhD2

Published Online: 27 JUL 2011

DOI: 10.1002/9781444346688.ch19

Inflammation and Allergy Drug Design

Inflammation and Allergy Drug Design

How to Cite

Berkman, N. and Levi-Schaffer, F. (2011) Profibrotic and Angiogenic Factors in Asthma, in Inflammation and Allergy Drug Design (eds K. Izuhara, S. T. Holgate and M. Wills-Karp), Wiley-Blackwell, Oxford, UK. doi: 10.1002/9781444346688.ch19

Editor Information

  1. 3

    Department of Biomolecular Sciences, Division of Medical Biochemistry, Saga Medical School, Nabeshima, Saga, Japan

  2. 4

    School of Medicine, Allergy and Inflammation Research, Southampton General Hospital, University Medicine, Southampton, UK

  3. 5

    Division of Immunology, Cincinnati Children's Medical Center, Cincinnati, OH, USA

Author Information

  1. 1

    Invasive Pulmonology, Institute of Pulmonology Medicine, Hadassah-Hebrew University Medical Center, Ein Kerem, Jerusalem, Israel

  2. 2

    Immunopharmacology Laboratory for Allergy and Asthma Research, Immunopharmacology, Institute for Drug Research, School of Pharmacy, Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel

Publication History

  1. Published Online: 27 JUL 2011
  2. Published Print: 13 AUG 2011

ISBN Information

Print ISBN: 9781444330144

Online ISBN: 9781444346688



  • profibrotic and - angiogenic factors in asthma;
  • airway remodeling, prominent pathophysiologic - feature of chronic asthma;
  • airway hyperresponsiveness (AHR) - component of asthma, optimal anti-inflammatory therapy;
  • asthma and airway fibrosis - increase in fibroblasts, differentiation of myofibroblasts in asthma;
  • transforming growth factor beta - TGF-β superfamily, over 30 different proteins and BMPs;
  • transforming growth factor beta - critical for embryogenesis and tissue repair, role in mediating immune responses;
  • eosinophils and angiogenesis - eosinophil contribution to angiogenesis, in asthma;
  • attenuation of angiogenesis - and cancer therapies, VEGF pathway as key regulator of angiogenesis;
  • interleukin 4 and interleukin 13 - cytokines from Th2 cells, mediators in asthma;
  • nerve growth factor (NGF), important neurotrophic agent - produced in airways


Airway remodeling is present in the bronchi of asthmatics and may account for poor response to treatment in individuals with refractory disease. Fibrosis and angiogenesis are key features of remodeling. Multiple factors present in the asthmatic airway contribute to fibrosis and angiogenesis and are therefore potential targets for the development of new antiremodeling therapies. We review the major profibrotic factors that contribute to remodeling in asthma, including transforming growth factor β, platelet-derived growth factor, fibroblast growth factor, epidermal growth factor, connective tissue growth factor, interleukin 13, endothelin, osteopontin, eotaxins, and extracellular matrix components such as fibronectin. Angiogenic factors include vascular endothelial growth factor, nerve growth factor, angiopoeitin, angiogenin, and endothelin. Mention is also made of endogenous inhibitors of angiogenesis, namely angiostatin and endostatin. For each factor, we review the biology and evidence that they are involved in asthma, and discuss these molecules as potential new therapeutic targets. We also briefly review the contribution of eosinophils to angiogenesis in asthma.