title: Blockade of the epidermal growth factor receptor decreases intimal hyperplasia in balloon-injured rat carotid artery.
abstract: OBJECTIVE
  Arterial intimal hyperplasia is induced by injury and is frequently the cause of luminal narrowing after vascular reconstruction. Smooth muscle cells (SMC) respond to injury by proliferating and migrating into the intima. This process is regulated by thrombin, endothelin, and angiotensin II, all ligands of G protein-coupled receptors. Signal transduction from these receptors in cultured cells depends in part on transactivation of epidermal growth factor receptor (EGFR). We hypothesize that EGFR has a substantial role in activation of SMC in vivo and development of intimal hyperplasia.
  
  
  METHODS
  Intimal hyperplasia was induced in rat carotid arteries by passage of a balloon catheter. Animals were given a monoclonal blocking antibody to rat EGFR, matched mouse immunoglobulin G (IgG) control antibody, or saline solution.
  
  
  RESULTS
  Blocking EGFR antibody inhibited medial SMC proliferation, as determined by 5-bromo-2'-deoxyuridine labeling at 2 days (IgG control, 8.0% +/- 2.0%; anti-EGFR, 3.2% +/- 0.8%) and intimal hyperplasia at 14 days (intimal area: IgG control, 0.07 +/- 0.01 mm(2); anti-EGFR, 0.04 +/- 0.01 mm(2)).
  
  
  CONCLUSIONS
  Activation of EGFR is important for early induction of SMC proliferation and subsequent intimal thickening.
authors.affiliation: Department of Surgery, University of Washington, 1959 Pacific Street NE, Seattle, WA 98195-6410, USA.
authors.forename: Allen K
authors.initials: AK
authors.lastname: Chan
authors.forename: Andreas
authors.initials: A
authors.lastname: Kalmes
authors.forename: Suzanne
authors.initials: S
authors.lastname: Hawkins
authors.forename: Günter
authors.initials: G
authors.lastname: Daum
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Clowes
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D020212:Carotid Artery Injuries / Q000473:pathology*; D017536:Carotid Artery, Common / Q000473:pathology*; D002404:Catheterization; D002455:Cell Division; D066246:ErbB Receptors / Q000276:immunology / Q000502:physiology*; D006965:Hyperplasia; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology*
chemical_list: D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D066246:ErbB Receptors