Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury

E. Dai, M. Stewart, B. Ritchie, Nasrin Mesaeli, S. Raha, D. Kolodziejczyk, M. Lundstrom Hobman, L. Y. Liu, W. Etches, N. Nation, M. Michalak, A. Lucas

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Both thrombotic and inflammatory responses to arterial injury have been implicated in atherosclerotic plaque growth. Calreticulin is a ubiquitous calcium-binding protein with antithrombotic activity and, in addition, is associated with leukocyte activation. We are investigating calreticulin as a potential vascular regulatory protein. The development of intimal hyperplasia was studied at sites of balloon injury in iliofemoral arteries from 91 rats. Calreticulin was infused directly into the artery immediately before balloon injury, and plaque growth was then assessed at 4 weeks' follow-up. Parallel studies of the effects of each calreticulin domain as well as a related calcium-binding protein, calsequestrin, were examined. The effects of calreticulin on platelet activation, clot formation, and mononuclear cell migration were also studied. When infused before balloon injury in rat iliofemoral arteries, calreticulin, or its high-capacity Ca2+-binding C domain, significantly reduces plaque development, whereas calsequestrin, a related calcium-binding protein that lacks the multifunctional nature of calreticulin, does not decrease plaque area (saline: 0.037±0.007 mm2, calsequestrin: 0.042±0.021 mm2, calreticulin: 0.003±0.002 mm2, n=46, P<.04). The N domain and more specifically the P domain, a low-capacity, high-affinity calcium-binding domain in calreticulin do not reduce intimal hyperplasia (N+P domain: 0.038±0.012 mm2, C domain: 0.003±0.002 mm2, n=45 rats, P<.0001). Calreticulin reduces macrophage and T cell staining in the arterial wall after injury but has no direct effect on monocyte migration in vitro (percent medial area staining positive for macrophage 24 hours after injury (N+P: 4.06±1.42, calreticulin: 0.273±0.02; n=26, P<.009). Calreticulin does, however, reduce platelet-dependent whole blood clotting time, in vitro (baseline: 78.23±2.04 seconds, calreticulin: 113.5±1.95 seconds; n=5, P<.002). We conclude that calreticulin significantly reduces intimal hyperplasia after arterial injury, potentially acting as a vascular regulatory protein.

Original languageEnglish
Pages (from-to)2359-2368
Number of pages10
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume17
Issue number11
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Tunica Intima
Calreticulin
Hyperplasia
Blood Vessels
Wounds and Injuries
Proteins
Calsequestrin
Calcium-Binding Proteins
Arteries
Macrophages
Staining and Labeling
Platelet Activation
Blood Coagulation
Atherosclerotic Plaques
Growth

Keywords

  • Atherosclerosis
  • Calreticulin
  • Monocytes
  • Thrombosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury. / Dai, E.; Stewart, M.; Ritchie, B.; Mesaeli, Nasrin; Raha, S.; Kolodziejczyk, D.; Lundstrom Hobman, M.; Liu, L. Y.; Etches, W.; Nation, N.; Michalak, M.; Lucas, A.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 17, No. 11, 1997, p. 2359-2368.

Research output: Contribution to journalArticle

Dai, E, Stewart, M, Ritchie, B, Mesaeli, N, Raha, S, Kolodziejczyk, D, Lundstrom Hobman, M, Liu, LY, Etches, W, Nation, N, Michalak, M & Lucas, A 1997, 'Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 17, no. 11, pp. 2359-2368.
Dai, E. ; Stewart, M. ; Ritchie, B. ; Mesaeli, Nasrin ; Raha, S. ; Kolodziejczyk, D. ; Lundstrom Hobman, M. ; Liu, L. Y. ; Etches, W. ; Nation, N. ; Michalak, M. ; Lucas, A. / Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 1997 ; Vol. 17, No. 11. pp. 2359-2368.
@article{8da61344150c4a6eac2724b8cc11105f,
title = "Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury",
abstract = "Both thrombotic and inflammatory responses to arterial injury have been implicated in atherosclerotic plaque growth. Calreticulin is a ubiquitous calcium-binding protein with antithrombotic activity and, in addition, is associated with leukocyte activation. We are investigating calreticulin as a potential vascular regulatory protein. The development of intimal hyperplasia was studied at sites of balloon injury in iliofemoral arteries from 91 rats. Calreticulin was infused directly into the artery immediately before balloon injury, and plaque growth was then assessed at 4 weeks' follow-up. Parallel studies of the effects of each calreticulin domain as well as a related calcium-binding protein, calsequestrin, were examined. The effects of calreticulin on platelet activation, clot formation, and mononuclear cell migration were also studied. When infused before balloon injury in rat iliofemoral arteries, calreticulin, or its high-capacity Ca2+-binding C domain, significantly reduces plaque development, whereas calsequestrin, a related calcium-binding protein that lacks the multifunctional nature of calreticulin, does not decrease plaque area (saline: 0.037±0.007 mm2, calsequestrin: 0.042±0.021 mm2, calreticulin: 0.003±0.002 mm2, n=46, P<.04). The N domain and more specifically the P domain, a low-capacity, high-affinity calcium-binding domain in calreticulin do not reduce intimal hyperplasia (N+P domain: 0.038±0.012 mm2, C domain: 0.003±0.002 mm2, n=45 rats, P<.0001). Calreticulin reduces macrophage and T cell staining in the arterial wall after injury but has no direct effect on monocyte migration in vitro (percent medial area staining positive for macrophage 24 hours after injury (N+P: 4.06±1.42, calreticulin: 0.273±0.02; n=26, P<.009). Calreticulin does, however, reduce platelet-dependent whole blood clotting time, in vitro (baseline: 78.23±2.04 seconds, calreticulin: 113.5±1.95 seconds; n=5, P<.002). We conclude that calreticulin significantly reduces intimal hyperplasia after arterial injury, potentially acting as a vascular regulatory protein.",
keywords = "Atherosclerosis, Calreticulin, Monocytes, Thrombosis",
author = "E. Dai and M. Stewart and B. Ritchie and Nasrin Mesaeli and S. Raha and D. Kolodziejczyk and {Lundstrom Hobman}, M. and Liu, {L. Y.} and W. Etches and N. Nation and M. Michalak and A. Lucas",
year = "1997",
language = "English",
volume = "17",
pages = "2359--2368",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "11",

}

TY - JOUR

T1 - Calreticulin, a potential vascular regulatory protein, reduces intimal hyperplasia after arterial injury

AU - Dai, E.

AU - Stewart, M.

AU - Ritchie, B.

AU - Mesaeli, Nasrin

AU - Raha, S.

AU - Kolodziejczyk, D.

AU - Lundstrom Hobman, M.

AU - Liu, L. Y.

AU - Etches, W.

AU - Nation, N.

AU - Michalak, M.

AU - Lucas, A.

PY - 1997

Y1 - 1997

N2 - Both thrombotic and inflammatory responses to arterial injury have been implicated in atherosclerotic plaque growth. Calreticulin is a ubiquitous calcium-binding protein with antithrombotic activity and, in addition, is associated with leukocyte activation. We are investigating calreticulin as a potential vascular regulatory protein. The development of intimal hyperplasia was studied at sites of balloon injury in iliofemoral arteries from 91 rats. Calreticulin was infused directly into the artery immediately before balloon injury, and plaque growth was then assessed at 4 weeks' follow-up. Parallel studies of the effects of each calreticulin domain as well as a related calcium-binding protein, calsequestrin, were examined. The effects of calreticulin on platelet activation, clot formation, and mononuclear cell migration were also studied. When infused before balloon injury in rat iliofemoral arteries, calreticulin, or its high-capacity Ca2+-binding C domain, significantly reduces plaque development, whereas calsequestrin, a related calcium-binding protein that lacks the multifunctional nature of calreticulin, does not decrease plaque area (saline: 0.037±0.007 mm2, calsequestrin: 0.042±0.021 mm2, calreticulin: 0.003±0.002 mm2, n=46, P<.04). The N domain and more specifically the P domain, a low-capacity, high-affinity calcium-binding domain in calreticulin do not reduce intimal hyperplasia (N+P domain: 0.038±0.012 mm2, C domain: 0.003±0.002 mm2, n=45 rats, P<.0001). Calreticulin reduces macrophage and T cell staining in the arterial wall after injury but has no direct effect on monocyte migration in vitro (percent medial area staining positive for macrophage 24 hours after injury (N+P: 4.06±1.42, calreticulin: 0.273±0.02; n=26, P<.009). Calreticulin does, however, reduce platelet-dependent whole blood clotting time, in vitro (baseline: 78.23±2.04 seconds, calreticulin: 113.5±1.95 seconds; n=5, P<.002). We conclude that calreticulin significantly reduces intimal hyperplasia after arterial injury, potentially acting as a vascular regulatory protein.

AB - Both thrombotic and inflammatory responses to arterial injury have been implicated in atherosclerotic plaque growth. Calreticulin is a ubiquitous calcium-binding protein with antithrombotic activity and, in addition, is associated with leukocyte activation. We are investigating calreticulin as a potential vascular regulatory protein. The development of intimal hyperplasia was studied at sites of balloon injury in iliofemoral arteries from 91 rats. Calreticulin was infused directly into the artery immediately before balloon injury, and plaque growth was then assessed at 4 weeks' follow-up. Parallel studies of the effects of each calreticulin domain as well as a related calcium-binding protein, calsequestrin, were examined. The effects of calreticulin on platelet activation, clot formation, and mononuclear cell migration were also studied. When infused before balloon injury in rat iliofemoral arteries, calreticulin, or its high-capacity Ca2+-binding C domain, significantly reduces plaque development, whereas calsequestrin, a related calcium-binding protein that lacks the multifunctional nature of calreticulin, does not decrease plaque area (saline: 0.037±0.007 mm2, calsequestrin: 0.042±0.021 mm2, calreticulin: 0.003±0.002 mm2, n=46, P<.04). The N domain and more specifically the P domain, a low-capacity, high-affinity calcium-binding domain in calreticulin do not reduce intimal hyperplasia (N+P domain: 0.038±0.012 mm2, C domain: 0.003±0.002 mm2, n=45 rats, P<.0001). Calreticulin reduces macrophage and T cell staining in the arterial wall after injury but has no direct effect on monocyte migration in vitro (percent medial area staining positive for macrophage 24 hours after injury (N+P: 4.06±1.42, calreticulin: 0.273±0.02; n=26, P<.009). Calreticulin does, however, reduce platelet-dependent whole blood clotting time, in vitro (baseline: 78.23±2.04 seconds, calreticulin: 113.5±1.95 seconds; n=5, P<.002). We conclude that calreticulin significantly reduces intimal hyperplasia after arterial injury, potentially acting as a vascular regulatory protein.

KW - Atherosclerosis

KW - Calreticulin

KW - Monocytes

KW - Thrombosis

UR - http://www.scopus.com/inward/record.url?scp=17344365411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=17344365411&partnerID=8YFLogxK

M3 - Article

VL - 17

SP - 2359

EP - 2368

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 11

ER -