A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo

Yao Liang Tang, Keping Qian, Y. Clare Zhang, Leping Shen, M. Ian Phillips

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Objectives: The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. Background: When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector" system that amplifies cardioprotective gene expression. Methods: Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Results: Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. Conclusions: The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

Original languageEnglish (US)
Pages (from-to)251-263
Number of pages13
JournalJournal of Cardiovascular Pharmacology and Therapeutics
Volume10
Issue number4
DOIs
StatePublished - Dec 1 2005

Fingerprint

Heme Oxygenase-1
Reperfusion Injury
Ischemia
Reperfusion
Ventricular Remodeling
Genes
Genetic Therapy
Plasmids
Myocardial Reperfusion
Proteins
Recovery of Function
Myocardial Ischemia
Myocardium
Therapeutics
Hypoxia
Lipids
Gene Expression

Keywords

  • Inflammatory response
  • Ischemia-reperfusion injury
  • Vigilant heme oxygenase-1 vector

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo. / Tang, Yao Liang; Qian, Keping; Zhang, Y. Clare; Shen, Leping; Phillips, M. Ian.

In: Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 10, No. 4, 01.12.2005, p. 251-263.

Research output: Contribution to journalArticle

@article{ced6276ea71443d59a630cc6ff7d345c,
title = "A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo",
abstract = "Objectives: The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. Background: When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy {"}vigilant vector{"} system that amplifies cardioprotective gene expression. Methods: Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Results: Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. Conclusions: The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.",
keywords = "Inflammatory response, Ischemia-reperfusion injury, Vigilant heme oxygenase-1 vector",
author = "Tang, {Yao Liang} and Keping Qian and Zhang, {Y. Clare} and Leping Shen and Phillips, {M. Ian}",
year = "2005",
month = "12",
day = "1",
doi = "10.1177/107424840501000405",
language = "English (US)",
volume = "10",
pages = "251--263",
journal = "Journal of Cardiovascular Pharmacology and Therapeutics",
issn = "1074-2484",
publisher = "SAGE Publications Ltd",
number = "4",

}

TY - JOUR

T1 - A vigilant, hypoxia-regulated heme oxygenase-1 gene vector in the heart limits cardiac injury after ischemia-reperfusion in vivo

AU - Tang, Yao Liang

AU - Qian, Keping

AU - Zhang, Y. Clare

AU - Shen, Leping

AU - Phillips, M. Ian

PY - 2005/12/1

Y1 - 2005/12/1

N2 - Objectives: The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. Background: When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector" system that amplifies cardioprotective gene expression. Methods: Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Results: Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. Conclusions: The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

AB - Objectives: The effect of a cardiac specific, hypoxia-regulated, human heme oxygenase-1 (hHO-1) vector to provide cardioprotection from ischemia-reperfusion injury was assessed. Background: When myocardial ischemia and reperfusion is asymptomatic, the damaging effects are cumulative and patients miss timely treatment. A gene therapy approach that expresses therapeutic genes only when ischemia is experienced is a desirable strategy. We have developed a cardiac-specific, hypoxia-regulated gene therapy "vigilant vector" system that amplifies cardioprotective gene expression. Methods: Vigilant hHO-1 plasmids, LacZ plasmids, or saline (n = 40 per group) were injected into mouse heart 2 days in advance of ischemia-reperfusion injury. Animals were exposed to 60 minutes of ischemia followed by 24 hours of reperfusion. For that term (24 hours) effects, the protein levels of HO-1, inflammatory responses, apoptosis, and infarct size were determined. For long-term (3 week) effects, the left ventricular remodeling and recovery of cardiac function were assessed. Results: Ischemia-reperfusion resulted in a timely overexpression of HO-1 protein. Infarct size at 24 hours after ischemia-reperfusion was significantly reduced in the HO-1-treated animals compared with the LacZ-treated group or saline-treated group (P < .001). The reduction of infarct size was accompanied by a decrease in lipid peroxidant activity, inflammatory cell infiltration, and proapoptotic protein level in ischemia-reperfusion-injured myocardium. The long-term study demonstrated that timely, hypoxia-induced HO-1 overexpression is beneficial in conserving cardiac function and attenuating left ventricle remodelling. Conclusions: The vigilant HO-1 vector provides a protective therapy in the heart for reducing cellular damage during ischemia-reperfusion injury and preserving heart function.

KW - Inflammatory response

KW - Ischemia-reperfusion injury

KW - Vigilant heme oxygenase-1 vector

UR - http://www.scopus.com/inward/record.url?scp=29344459197&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=29344459197&partnerID=8YFLogxK

U2 - 10.1177/107424840501000405

DO - 10.1177/107424840501000405

M3 - Article

C2 - 16382261

AN - SCOPUS:29344459197

VL - 10

SP - 251

EP - 263

JO - Journal of Cardiovascular Pharmacology and Therapeutics

JF - Journal of Cardiovascular Pharmacology and Therapeutics

SN - 1074-2484

IS - 4

ER -