Transplant vasculopathy

Viral anti-inflammatory serpin regulation of atherogenesis

Alexandra Lucas, Erbin Dai, Liying Liu, Haiyan Guan, Piers Nash, Douglas McFadden, Leslie Miller

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Background: Surgical and ischemic injury to the artery wall initiates vascular wound-healing responses that stimulate atherosclerotic plaque growth. The plasminogen activators have cellular chemotactic, adhesion, and proteolytic activity. Serp-1 is a secreted myxoma virus glycoprotein serpin that binds and inhibits plasminogen activators. We have examined the effects of Serp-1 on plaque growth and inflammatory cell invasion in animal models after balloon injury and after aortic allograft transplant. Methods: We used histologic analysis to assess 4 animal models of angioplasty-mediated injury and 2 models of aortic allograft transplant for intimal hyperplasia and cellular invasion. We assessed plasminogen activator (uPA and tPA) and inhibitor (PAI-1) expression in rat iliofemoral arteries after balloon injury using Western blot, enzyme activity, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Plaque growth after balloon injury decreased after Serp-1 treatment in all balloon-injury models tested. Transplant vasculopathy also significantly decreased in 2 rat models of aortic allograft transplant. Infusion of a Serp-1 active site mutant, that lacked plasminogen activator inhibiting activity, did not inhibit plaque growth. Quantitative RT-PCR detected increased transcription of PAI-1 mRNA. Increased PAI-1 protein and enzyme-inhibitory activity was also detected in Serp-1-treated arteries by activity assay and Western blot. Conclusions: Thrombolytic serpins are central regulatory agents in vascular wound-healing responses. Investigation of the inhibitory mechanisms of viral serpins may provide new insights into atherogenesis.

Original languageEnglish (US)
Pages (from-to)1029-1038
Number of pages10
JournalJournal of Heart and Lung Transplantation
Volume19
Issue number11
DOIs
StatePublished - Nov 25 2000
Externally publishedYes

Fingerprint

Serpins
Plasminogen Activators
Atherosclerosis
Anti-Inflammatory Agents
Plasminogen Activator Inhibitor 1
Transplants
Wounds and Injuries
Allografts
Arteries
Growth
Reverse Transcriptase Polymerase Chain Reaction
Wound Healing
Blood Vessels
Myxoma virus
Animal Models
Western Blotting
Tunica Intima
Intraoperative Complications
Atherosclerotic Plaques
Enzymes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

Cite this

Transplant vasculopathy : Viral anti-inflammatory serpin regulation of atherogenesis. / Lucas, Alexandra; Dai, Erbin; Liu, Liying; Guan, Haiyan; Nash, Piers; McFadden, Douglas; Miller, Leslie.

In: Journal of Heart and Lung Transplantation, Vol. 19, No. 11, 25.11.2000, p. 1029-1038.

Research output: Contribution to journalArticle

Lucas, Alexandra ; Dai, Erbin ; Liu, Liying ; Guan, Haiyan ; Nash, Piers ; McFadden, Douglas ; Miller, Leslie. / Transplant vasculopathy : Viral anti-inflammatory serpin regulation of atherogenesis. In: Journal of Heart and Lung Transplantation. 2000 ; Vol. 19, No. 11. pp. 1029-1038.
@article{cd288ff3687347d499db3011d0896037,
title = "Transplant vasculopathy: Viral anti-inflammatory serpin regulation of atherogenesis",
abstract = "Background: Surgical and ischemic injury to the artery wall initiates vascular wound-healing responses that stimulate atherosclerotic plaque growth. The plasminogen activators have cellular chemotactic, adhesion, and proteolytic activity. Serp-1 is a secreted myxoma virus glycoprotein serpin that binds and inhibits plasminogen activators. We have examined the effects of Serp-1 on plaque growth and inflammatory cell invasion in animal models after balloon injury and after aortic allograft transplant. Methods: We used histologic analysis to assess 4 animal models of angioplasty-mediated injury and 2 models of aortic allograft transplant for intimal hyperplasia and cellular invasion. We assessed plasminogen activator (uPA and tPA) and inhibitor (PAI-1) expression in rat iliofemoral arteries after balloon injury using Western blot, enzyme activity, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Plaque growth after balloon injury decreased after Serp-1 treatment in all balloon-injury models tested. Transplant vasculopathy also significantly decreased in 2 rat models of aortic allograft transplant. Infusion of a Serp-1 active site mutant, that lacked plasminogen activator inhibiting activity, did not inhibit plaque growth. Quantitative RT-PCR detected increased transcription of PAI-1 mRNA. Increased PAI-1 protein and enzyme-inhibitory activity was also detected in Serp-1-treated arteries by activity assay and Western blot. Conclusions: Thrombolytic serpins are central regulatory agents in vascular wound-healing responses. Investigation of the inhibitory mechanisms of viral serpins may provide new insights into atherogenesis.",
author = "Alexandra Lucas and Erbin Dai and Liying Liu and Haiyan Guan and Piers Nash and Douglas McFadden and Leslie Miller",
year = "2000",
month = "11",
day = "25",
doi = "10.1016/S1053-2498(00)00190-X",
language = "English (US)",
volume = "19",
pages = "1029--1038",
journal = "Journal of Heart and Lung Transplantation",
issn = "1053-2498",
publisher = "Elsevier USA",
number = "11",

}

TY - JOUR

T1 - Transplant vasculopathy

T2 - Viral anti-inflammatory serpin regulation of atherogenesis

AU - Lucas, Alexandra

AU - Dai, Erbin

AU - Liu, Liying

AU - Guan, Haiyan

AU - Nash, Piers

AU - McFadden, Douglas

AU - Miller, Leslie

PY - 2000/11/25

Y1 - 2000/11/25

N2 - Background: Surgical and ischemic injury to the artery wall initiates vascular wound-healing responses that stimulate atherosclerotic plaque growth. The plasminogen activators have cellular chemotactic, adhesion, and proteolytic activity. Serp-1 is a secreted myxoma virus glycoprotein serpin that binds and inhibits plasminogen activators. We have examined the effects of Serp-1 on plaque growth and inflammatory cell invasion in animal models after balloon injury and after aortic allograft transplant. Methods: We used histologic analysis to assess 4 animal models of angioplasty-mediated injury and 2 models of aortic allograft transplant for intimal hyperplasia and cellular invasion. We assessed plasminogen activator (uPA and tPA) and inhibitor (PAI-1) expression in rat iliofemoral arteries after balloon injury using Western blot, enzyme activity, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Plaque growth after balloon injury decreased after Serp-1 treatment in all balloon-injury models tested. Transplant vasculopathy also significantly decreased in 2 rat models of aortic allograft transplant. Infusion of a Serp-1 active site mutant, that lacked plasminogen activator inhibiting activity, did not inhibit plaque growth. Quantitative RT-PCR detected increased transcription of PAI-1 mRNA. Increased PAI-1 protein and enzyme-inhibitory activity was also detected in Serp-1-treated arteries by activity assay and Western blot. Conclusions: Thrombolytic serpins are central regulatory agents in vascular wound-healing responses. Investigation of the inhibitory mechanisms of viral serpins may provide new insights into atherogenesis.

AB - Background: Surgical and ischemic injury to the artery wall initiates vascular wound-healing responses that stimulate atherosclerotic plaque growth. The plasminogen activators have cellular chemotactic, adhesion, and proteolytic activity. Serp-1 is a secreted myxoma virus glycoprotein serpin that binds and inhibits plasminogen activators. We have examined the effects of Serp-1 on plaque growth and inflammatory cell invasion in animal models after balloon injury and after aortic allograft transplant. Methods: We used histologic analysis to assess 4 animal models of angioplasty-mediated injury and 2 models of aortic allograft transplant for intimal hyperplasia and cellular invasion. We assessed plasminogen activator (uPA and tPA) and inhibitor (PAI-1) expression in rat iliofemoral arteries after balloon injury using Western blot, enzyme activity, and quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). Results: Plaque growth after balloon injury decreased after Serp-1 treatment in all balloon-injury models tested. Transplant vasculopathy also significantly decreased in 2 rat models of aortic allograft transplant. Infusion of a Serp-1 active site mutant, that lacked plasminogen activator inhibiting activity, did not inhibit plaque growth. Quantitative RT-PCR detected increased transcription of PAI-1 mRNA. Increased PAI-1 protein and enzyme-inhibitory activity was also detected in Serp-1-treated arteries by activity assay and Western blot. Conclusions: Thrombolytic serpins are central regulatory agents in vascular wound-healing responses. Investigation of the inhibitory mechanisms of viral serpins may provide new insights into atherogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0033763829&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033763829&partnerID=8YFLogxK

U2 - 10.1016/S1053-2498(00)00190-X

DO - 10.1016/S1053-2498(00)00190-X

M3 - Article

VL - 19

SP - 1029

EP - 1038

JO - Journal of Heart and Lung Transplantation

JF - Journal of Heart and Lung Transplantation

SN - 1053-2498

IS - 11

ER -