Erythropoietin increases expression and function of vascular copper-and zinc-containing superoxide dismutase

Livius V. D'Uscio, Leslie A. Smith, Zvonimir S Katusic

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper-and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.

Original languageEnglish (US)
Pages (from-to)998-1004
Number of pages7
JournalHypertension
Volume55
Issue number4
DOIs
StatePublished - Apr 2010

Fingerprint

Erythropoietin
Superoxide Dismutase
Blood Vessels
Zinc
Copper
Superoxides
Common Carotid Artery
Aorta
Oxidative Stress
Wounds and Injuries

Keywords

  • Erythropoietin
  • Mice
  • Protein kinase B
  • Superoxide anions
  • Superoxide dismutase 1
  • Vasculature

ASJC Scopus subject areas

  • Internal Medicine

Cite this

Erythropoietin increases expression and function of vascular copper-and zinc-containing superoxide dismutase. / D'Uscio, Livius V.; Smith, Leslie A.; Katusic, Zvonimir S.

In: Hypertension, Vol. 55, No. 4, 04.2010, p. 998-1004.

Research output: Contribution to journalArticle

@article{7e4aaa457c084b268077f82efeddae2d,
title = "Erythropoietin increases expression and function of vascular copper-and zinc-containing superoxide dismutase",
abstract = "Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper-and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.",
keywords = "Erythropoietin, Mice, Protein kinase B, Superoxide anions, Superoxide dismutase 1, Vasculature",
author = "D'Uscio, {Livius V.} and Smith, {Leslie A.} and Katusic, {Zvonimir S}",
year = "2010",
month = "4",
doi = "10.1161/HYPERTENSIONAHA.110.150623",
language = "English (US)",
volume = "55",
pages = "998--1004",
journal = "Hypertension",
issn = "0194-911X",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Erythropoietin increases expression and function of vascular copper-and zinc-containing superoxide dismutase

AU - D'Uscio, Livius V.

AU - Smith, Leslie A.

AU - Katusic, Zvonimir S

PY - 2010/4

Y1 - 2010/4

N2 - Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper-and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.

AB - Previous studies have shown that treatment with erythropoietin (EPO) exerts vascular protective effects. The exact mechanisms responsible for these effects are not completely understood. In the present study, we hypothesized that EPO stimulates expression and activity of copper-and zinc-containing superoxide dismutase (SOD1), thus protecting vascular tissue from oxidative stress induced by excessive concentrations of superoxide anions. EPO treatment of wild-type mice for 2 weeks (1000 U/kg, SC, biweekly) significantly increased aortic expression of SOD1. This effect resulted in a significant reduction of superoxide anion concentrations in aorta of treated mice. The ability of EPO to reduce vascular production of superoxide anions was abolished in SOD1-deficient mice. In a mouse model of wire-induced injury of the common carotid artery, treatment of wild-type mice with EPO prevented pathological remodeling, whereas the vascular effect of EPO was absent in SOD1-deficient mice. Our findings demonstrate that treatment with EPO increases vascular expression of SOD1. This effect appears to be an important molecular mechanism underlying vascular protection by EPO.

KW - Erythropoietin

KW - Mice

KW - Protein kinase B

KW - Superoxide anions

KW - Superoxide dismutase 1

KW - Vasculature

UR - http://www.scopus.com/inward/record.url?scp=77950502455&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77950502455&partnerID=8YFLogxK

U2 - 10.1161/HYPERTENSIONAHA.110.150623

DO - 10.1161/HYPERTENSIONAHA.110.150623

M3 - Article

C2 - 20194292

AN - SCOPUS:77950502455

VL - 55

SP - 998

EP - 1004

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 4

ER -