The role of hyaluronan and its receptors in restenosis after balloon angioplasty

Development of a potential therapy

R. C. Savani, E. A. Turley

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Atherosclerosis is a progressive condition that is initiated by endothelial injury, promoted by growth factors, and which results in the formation of fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is used to dilate these plaques in the coronary circulation so as to prevent occlusion of this critical blood supply. However, 30-50% of balloon dilatations end in restenosis within six months of the procedure. The pathogenesis of both atherosclerosis and restenosis after balloon angioplasty involves the migration of medial smooth-muscle cells across the internal elastic lamina to form a neointima. Proliferation of these cells and their elaboration of an extracellular matrix results in stenosis of the affected area. Investigation of several animal models, as well as of the human condition, indicates the presence of an ongoing inflammatory reaction involving T cells and other leukocytes which probably maintain smooth-muscle cell migration, proliferation and matrix deposition. We have shown that the stenotic response involves the expression of HA (hyaluronan) receptors on both the infiltrating white cells and on smooth-muscle cell populations. Thus, in vitro, the locomotion and chemotaxis of these cells in response to injury is inhibited by reagents that block HA-receptor interactions including HA-binding peptides and high doses of HA. Further, the expression of these HA receptors is up-regulated after balloon-catheter injury of the rat carotid artery, and exposure of injured arteries to high concentrations of HA in vivo results in significant inhibition of neointimal formation. The possible clinical benefits of this response are discussed.

Original languageEnglish (US)
Pages (from-to)141-151
Number of pages11
JournalInternational Journal of Tissue Reactions
Volume17
Issue number4
StatePublished - 1995

Fingerprint

CD44 Antigens
Balloon Angioplasty
Hyaluronic Acid
Smooth Muscle Myocytes
Cell Movement
Atherosclerosis
Cell Proliferation
Carotid Artery Injuries
Neointima
Coronary Circulation
Wounds and Injuries
Chemotaxis
Extracellular Matrix
Blood Vessels
Dilatation
Intercellular Signaling Peptides and Proteins
Pathologic Constriction
Leukocytes
Therapeutics
Catheters

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

@article{b56ea6a1120a4ff09a710f74c19760be,
title = "The role of hyaluronan and its receptors in restenosis after balloon angioplasty: Development of a potential therapy",
abstract = "Atherosclerosis is a progressive condition that is initiated by endothelial injury, promoted by growth factors, and which results in the formation of fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is used to dilate these plaques in the coronary circulation so as to prevent occlusion of this critical blood supply. However, 30-50{\%} of balloon dilatations end in restenosis within six months of the procedure. The pathogenesis of both atherosclerosis and restenosis after balloon angioplasty involves the migration of medial smooth-muscle cells across the internal elastic lamina to form a neointima. Proliferation of these cells and their elaboration of an extracellular matrix results in stenosis of the affected area. Investigation of several animal models, as well as of the human condition, indicates the presence of an ongoing inflammatory reaction involving T cells and other leukocytes which probably maintain smooth-muscle cell migration, proliferation and matrix deposition. We have shown that the stenotic response involves the expression of HA (hyaluronan) receptors on both the infiltrating white cells and on smooth-muscle cell populations. Thus, in vitro, the locomotion and chemotaxis of these cells in response to injury is inhibited by reagents that block HA-receptor interactions including HA-binding peptides and high doses of HA. Further, the expression of these HA receptors is up-regulated after balloon-catheter injury of the rat carotid artery, and exposure of injured arteries to high concentrations of HA in vivo results in significant inhibition of neointimal formation. The possible clinical benefits of this response are discussed.",
author = "Savani, {R. C.} and Turley, {E. A.}",
year = "1995",
language = "English (US)",
volume = "17",
pages = "141--151",
journal = "International Journal of Tissue Reactions",
issn = "0250-0868",
publisher = "Bioscience Ediprint Inc.",
number = "4",

}

TY - JOUR

T1 - The role of hyaluronan and its receptors in restenosis after balloon angioplasty

T2 - Development of a potential therapy

AU - Savani, R. C.

AU - Turley, E. A.

PY - 1995

Y1 - 1995

N2 - Atherosclerosis is a progressive condition that is initiated by endothelial injury, promoted by growth factors, and which results in the formation of fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is used to dilate these plaques in the coronary circulation so as to prevent occlusion of this critical blood supply. However, 30-50% of balloon dilatations end in restenosis within six months of the procedure. The pathogenesis of both atherosclerosis and restenosis after balloon angioplasty involves the migration of medial smooth-muscle cells across the internal elastic lamina to form a neointima. Proliferation of these cells and their elaboration of an extracellular matrix results in stenosis of the affected area. Investigation of several animal models, as well as of the human condition, indicates the presence of an ongoing inflammatory reaction involving T cells and other leukocytes which probably maintain smooth-muscle cell migration, proliferation and matrix deposition. We have shown that the stenotic response involves the expression of HA (hyaluronan) receptors on both the infiltrating white cells and on smooth-muscle cell populations. Thus, in vitro, the locomotion and chemotaxis of these cells in response to injury is inhibited by reagents that block HA-receptor interactions including HA-binding peptides and high doses of HA. Further, the expression of these HA receptors is up-regulated after balloon-catheter injury of the rat carotid artery, and exposure of injured arteries to high concentrations of HA in vivo results in significant inhibition of neointimal formation. The possible clinical benefits of this response are discussed.

AB - Atherosclerosis is a progressive condition that is initiated by endothelial injury, promoted by growth factors, and which results in the formation of fibrofatty plaques that narrow the affected blood vessel. Balloon angioplasty is used to dilate these plaques in the coronary circulation so as to prevent occlusion of this critical blood supply. However, 30-50% of balloon dilatations end in restenosis within six months of the procedure. The pathogenesis of both atherosclerosis and restenosis after balloon angioplasty involves the migration of medial smooth-muscle cells across the internal elastic lamina to form a neointima. Proliferation of these cells and their elaboration of an extracellular matrix results in stenosis of the affected area. Investigation of several animal models, as well as of the human condition, indicates the presence of an ongoing inflammatory reaction involving T cells and other leukocytes which probably maintain smooth-muscle cell migration, proliferation and matrix deposition. We have shown that the stenotic response involves the expression of HA (hyaluronan) receptors on both the infiltrating white cells and on smooth-muscle cell populations. Thus, in vitro, the locomotion and chemotaxis of these cells in response to injury is inhibited by reagents that block HA-receptor interactions including HA-binding peptides and high doses of HA. Further, the expression of these HA receptors is up-regulated after balloon-catheter injury of the rat carotid artery, and exposure of injured arteries to high concentrations of HA in vivo results in significant inhibition of neointimal formation. The possible clinical benefits of this response are discussed.

UR - http://www.scopus.com/inward/record.url?scp=0029617369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029617369&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 141

EP - 151

JO - International Journal of Tissue Reactions

JF - International Journal of Tissue Reactions

SN - 0250-0868

IS - 4

ER -