Blockade of the epidermal growth factor receptor decreases intimal hyperplasia in balloon-injured rat carotid artery.
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.
Chan
Allen K
AK
Department of Surgery, University of Washington, 1959 Pacific Street NE, Seattle, WA 98195-6410, USA.
Kalmes
Andreas
A
Hawkins
Suzanne
S
Daum
Günter
G
Clowes
Alexander W
AW
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*
D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D066246:ErbB Receptors