Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice

Eugenio Stabile, Mary Susan Burnett, Craig Watkins, Timothy Kinnaird, Alessia Bachis, Andrea La Sala, Jonathan M. Miller, Matie Shou, Stephen E. Epstein, Shmuel Fuchs

Research output: Contribution to journalArticle

158 Citations (Scopus)

Abstract

Background - T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. Methods and Results - One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. Conclusions - These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.

Original languageEnglish
Pages (from-to)205-210
Number of pages6
JournalCirculation
Volume108
Issue number2
DOIs
Publication statusPublished - Jul 15 2003

Fingerprint

Hindlimb
Knockout Mice
Ischemia
T-Lymphocytes
Macrophages
Muscles
Vascular Endothelial Growth Factor A
Immune System
Muscular Atrophy
Recovery of Function
Atherosclerotic Plaques
Pathologic Processes
Femoral Artery
Wound Healing
Ligation
Catalytic Domain
Fibrosis
Spleen
Extremities
Arteries

Keywords

  • Angiogenesis
  • Inflammation
  • Lymphocytes

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Stabile, E., Susan Burnett, M., Watkins, C., Kinnaird, T., Bachis, A., La Sala, A., ... Fuchs, S. (2003). Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice. Circulation, 108(2), 205-210. https://doi.org/10.1161/01.CIR.0000079225.50817.71

Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice. / Stabile, Eugenio; Susan Burnett, Mary; Watkins, Craig; Kinnaird, Timothy; Bachis, Alessia; La Sala, Andrea; Miller, Jonathan M.; Shou, Matie; Epstein, Stephen E.; Fuchs, Shmuel.

In: Circulation, Vol. 108, No. 2, 15.07.2003, p. 205-210.

Research output: Contribution to journalArticle

Stabile, E, Susan Burnett, M, Watkins, C, Kinnaird, T, Bachis, A, La Sala, A, Miller, JM, Shou, M, Epstein, SE & Fuchs, S 2003, 'Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice', Circulation, vol. 108, no. 2, pp. 205-210. https://doi.org/10.1161/01.CIR.0000079225.50817.71
Stabile E, Susan Burnett M, Watkins C, Kinnaird T, Bachis A, La Sala A et al. Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice. Circulation. 2003 Jul 15;108(2):205-210. https://doi.org/10.1161/01.CIR.0000079225.50817.71
Stabile, Eugenio ; Susan Burnett, Mary ; Watkins, Craig ; Kinnaird, Timothy ; Bachis, Alessia ; La Sala, Andrea ; Miller, Jonathan M. ; Shou, Matie ; Epstein, Stephen E. ; Fuchs, Shmuel. / Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice. In: Circulation. 2003 ; Vol. 108, No. 2. pp. 205-210.
@article{0f5ce4ec3bc04f648b5d02df8d17ea1a,
title = "Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice",
abstract = "Background - T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. Methods and Results - One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. Conclusions - These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25{\%} decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.",
keywords = "Angiogenesis, Inflammation, Lymphocytes",
author = "Eugenio Stabile and {Susan Burnett}, Mary and Craig Watkins and Timothy Kinnaird and Alessia Bachis and {La Sala}, Andrea and Miller, {Jonathan M.} and Matie Shou and Epstein, {Stephen E.} and Shmuel Fuchs",
year = "2003",
month = "7",
day = "15",
doi = "10.1161/01.CIR.0000079225.50817.71",
language = "English",
volume = "108",
pages = "205--210",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "2",

}

TY - JOUR

T1 - Impaired arteriogenic response to acute hindlimb ischemia in CD4-knockout mice

AU - Stabile, Eugenio

AU - Susan Burnett, Mary

AU - Watkins, Craig

AU - Kinnaird, Timothy

AU - Bachis, Alessia

AU - La Sala, Andrea

AU - Miller, Jonathan M.

AU - Shou, Matie

AU - Epstein, Stephen E.

AU - Fuchs, Shmuel

PY - 2003/7/15

Y1 - 2003/7/15

N2 - Background - T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. Methods and Results - One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. Conclusions - These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.

AB - Background - T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. Methods and Results - One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. Conclusions - These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.

KW - Angiogenesis

KW - Inflammation

KW - Lymphocytes

UR - http://www.scopus.com/inward/record.url?scp=0038108603&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0038108603&partnerID=8YFLogxK

U2 - 10.1161/01.CIR.0000079225.50817.71

DO - 10.1161/01.CIR.0000079225.50817.71

M3 - Article

C2 - 12821542

AN - SCOPUS:0038108603

VL - 108

SP - 205

EP - 210

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 2

ER -