Periadventitial inducible nitric oxide synthase expression and intimal thickening

Guido R Y De Meyer, Mark M. Kockx, Kristel M. Cromheeke, Cheikh Seye, Arnold G. Herman, Hidde Bult

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

Positioning a silicone collar around the rabbit carotid artery induces a smooth muscle cell-rich intimal thickening. We investigated the localization of inducible nitric oxide synthase (iNOS) during thickening of the intima, the effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18 hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for iNOS, including naive, sham-operated, and carotid arteries in which ox-LDL had been infused locally for 14 days. Furthermore, collars were connected to osmotic minipumps for local delivery (5μL · h-1, 14 days, n= 12) of saline or the iNOS inhibitor L-N6-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the adventitia and the periadventitial granulation tissue of collared arteries, iNOS-positive macrophages and T lymphocytes were present from 18 hours onward. The media and intima were negative for iNOS. Reverse transcription-polymerase chain reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine staining. Ox-LDL-treated arteries, which had a thicker intima, showed a pronounced influx of macrophages and T lymphocytes in all layers of the vessel wall, accompanied by iNOS expression in a subpopulation of these cells. Our study indicates that iNOS was not induced in intimal thickenings predominantly consisting of smooth muscle cells. However, iNOS was expressed in (peri)adventitial tissue and counteracted the progression of intimal thickening. Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive macrophages and T lymphocytes in the vessel, but this could not prevent the progression of intimal thickening.

Original languageEnglish (US)
Pages (from-to)1896-1902
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume20
Issue number8
StatePublished - 2000
Externally publishedYes

Fingerprint

Tunica Intima
Nitric Oxide Synthase Type II
Adventitia
Arteries
Macrophages
T-Lymphocytes
Carotid Arteries
Smooth Muscle Myocytes
Granulation Tissue
Silicones

Keywords

  • Adventitia
  • Intima
  • Local delivery
  • Nitric oxide
  • Oxidized LDL

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

De Meyer, G. R. Y., Kockx, M. M., Cromheeke, K. M., Seye, C., Herman, A. G., & Bult, H. (2000). Periadventitial inducible nitric oxide synthase expression and intimal thickening. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(8), 1896-1902.

Periadventitial inducible nitric oxide synthase expression and intimal thickening. / De Meyer, Guido R Y; Kockx, Mark M.; Cromheeke, Kristel M.; Seye, Cheikh; Herman, Arnold G.; Bult, Hidde.

In: Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 20, No. 8, 2000, p. 1896-1902.

Research output: Contribution to journalArticle

De Meyer, GRY, Kockx, MM, Cromheeke, KM, Seye, C, Herman, AG & Bult, H 2000, 'Periadventitial inducible nitric oxide synthase expression and intimal thickening', Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 20, no. 8, pp. 1896-1902.
De Meyer, Guido R Y ; Kockx, Mark M. ; Cromheeke, Kristel M. ; Seye, Cheikh ; Herman, Arnold G. ; Bult, Hidde. / Periadventitial inducible nitric oxide synthase expression and intimal thickening. In: Arteriosclerosis, Thrombosis, and Vascular Biology. 2000 ; Vol. 20, No. 8. pp. 1896-1902.
@article{a7cca199aa99403caccc3639e30c4911,
title = "Periadventitial inducible nitric oxide synthase expression and intimal thickening",
abstract = "Positioning a silicone collar around the rabbit carotid artery induces a smooth muscle cell-rich intimal thickening. We investigated the localization of inducible nitric oxide synthase (iNOS) during thickening of the intima, the effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18 hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for iNOS, including naive, sham-operated, and carotid arteries in which ox-LDL had been infused locally for 14 days. Furthermore, collars were connected to osmotic minipumps for local delivery (5μL · h-1, 14 days, n= 12) of saline or the iNOS inhibitor L-N6-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the adventitia and the periadventitial granulation tissue of collared arteries, iNOS-positive macrophages and T lymphocytes were present from 18 hours onward. The media and intima were negative for iNOS. Reverse transcription-polymerase chain reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine staining. Ox-LDL-treated arteries, which had a thicker intima, showed a pronounced influx of macrophages and T lymphocytes in all layers of the vessel wall, accompanied by iNOS expression in a subpopulation of these cells. Our study indicates that iNOS was not induced in intimal thickenings predominantly consisting of smooth muscle cells. However, iNOS was expressed in (peri)adventitial tissue and counteracted the progression of intimal thickening. Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive macrophages and T lymphocytes in the vessel, but this could not prevent the progression of intimal thickening.",
keywords = "Adventitia, Intima, Local delivery, Nitric oxide, Oxidized LDL",
author = "{De Meyer}, {Guido R Y} and Kockx, {Mark M.} and Cromheeke, {Kristel M.} and Cheikh Seye and Herman, {Arnold G.} and Hidde Bult",
year = "2000",
language = "English (US)",
volume = "20",
pages = "1896--1902",
journal = "Arteriosclerosis, Thrombosis, and Vascular Biology",
issn = "1079-5642",
publisher = "Lippincott Williams and Wilkins",
number = "8",

}

TY - JOUR

T1 - Periadventitial inducible nitric oxide synthase expression and intimal thickening

AU - De Meyer, Guido R Y

AU - Kockx, Mark M.

AU - Cromheeke, Kristel M.

AU - Seye, Cheikh

AU - Herman, Arnold G.

AU - Bult, Hidde

PY - 2000

Y1 - 2000

N2 - Positioning a silicone collar around the rabbit carotid artery induces a smooth muscle cell-rich intimal thickening. We investigated the localization of inducible nitric oxide synthase (iNOS) during thickening of the intima, the effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18 hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for iNOS, including naive, sham-operated, and carotid arteries in which ox-LDL had been infused locally for 14 days. Furthermore, collars were connected to osmotic minipumps for local delivery (5μL · h-1, 14 days, n= 12) of saline or the iNOS inhibitor L-N6-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the adventitia and the periadventitial granulation tissue of collared arteries, iNOS-positive macrophages and T lymphocytes were present from 18 hours onward. The media and intima were negative for iNOS. Reverse transcription-polymerase chain reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine staining. Ox-LDL-treated arteries, which had a thicker intima, showed a pronounced influx of macrophages and T lymphocytes in all layers of the vessel wall, accompanied by iNOS expression in a subpopulation of these cells. Our study indicates that iNOS was not induced in intimal thickenings predominantly consisting of smooth muscle cells. However, iNOS was expressed in (peri)adventitial tissue and counteracted the progression of intimal thickening. Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive macrophages and T lymphocytes in the vessel, but this could not prevent the progression of intimal thickening.

AB - Positioning a silicone collar around the rabbit carotid artery induces a smooth muscle cell-rich intimal thickening. We investigated the localization of inducible nitric oxide synthase (iNOS) during thickening of the intima, the effect of iNOS inhibition on intimal thickness, and the effect of oxidized LDL (ox-LDL) on iNOS expression in the vessel wall. Collars were positioned for 18 hours or for 3, 7, or 14 days. Arterial cross sections were immunostained for iNOS, including naive, sham-operated, and carotid arteries in which ox-LDL had been infused locally for 14 days. Furthermore, collars were connected to osmotic minipumps for local delivery (5μL · h-1, 14 days, n= 12) of saline or the iNOS inhibitor L-N6-(1-iminoethyl)-lysine-HCl (L-NIL, 10 mmol/L). In the adventitia and the periadventitial granulation tissue of collared arteries, iNOS-positive macrophages and T lymphocytes were present from 18 hours onward. The media and intima were negative for iNOS. Reverse transcription-polymerase chain reaction revealed iNOS mRNA in collared but not in sham-operated arteries. Local inhibition of iNOS doubled the intimal thickness and decreased nitrotyrosine staining. Ox-LDL-treated arteries, which had a thicker intima, showed a pronounced influx of macrophages and T lymphocytes in all layers of the vessel wall, accompanied by iNOS expression in a subpopulation of these cells. Our study indicates that iNOS was not induced in intimal thickenings predominantly consisting of smooth muscle cells. However, iNOS was expressed in (peri)adventitial tissue and counteracted the progression of intimal thickening. Ox-LDL treatment was accompanied by an abundant influx of iNOS-positive macrophages and T lymphocytes in the vessel, but this could not prevent the progression of intimal thickening.

KW - Adventitia

KW - Intima

KW - Local delivery

KW - Nitric oxide

KW - Oxidized LDL

UR - http://www.scopus.com/inward/record.url?scp=0033883808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033883808&partnerID=8YFLogxK

M3 - Article

VL - 20

SP - 1896

EP - 1902

JO - Arteriosclerosis, Thrombosis, and Vascular Biology

JF - Arteriosclerosis, Thrombosis, and Vascular Biology

SN - 1079-5642

IS - 8

ER -