Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model

Andrew J. Carter, John R. Laird, Andrew Farb, William Kufs, Dale C. Wortham, Renu Virmani

Research output: Contribution to journalArticle

212 Citations (Scopus)

Abstract

Objectives. This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. Background. Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. Methods. Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. Results. The area of thrombus was minimal at 24 h ([mean ± SE] 0.44 ± 0.12 mm2). Neointimal area at 7 days (0.72 ± 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 ± 0.39 mm2) and 28 days (3.30 ± 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 ± 3.5% at 7 days compared with 9.6 ± 1.3% by 14 days (p = 0.0247) and declined to 1.1 ± 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days). Conclusions. Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.

Original languageEnglish (US)
Pages (from-to)1398-1405
Number of pages8
JournalJournal of the American College of Cardiology
Volume24
Issue number5
DOIs
StatePublished - Nov 1 1994
Externally publishedYes

Fingerprint

Smooth Muscle Myocytes
Thrombosis
Swine
Cell Proliferation
Stents
Wounds and Injuries
Sus scrofa
Proliferating Cell Nuclear Antigen
Coronary Vessels
Animal Models
Arteries
Monoclonal Antibodies

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model. / Carter, Andrew J.; Laird, John R.; Farb, Andrew; Kufs, William; Wortham, Dale C.; Virmani, Renu.

In: Journal of the American College of Cardiology, Vol. 24, No. 5, 01.11.1994, p. 1398-1405.

Research output: Contribution to journalArticle

Carter, Andrew J. ; Laird, John R. ; Farb, Andrew ; Kufs, William ; Wortham, Dale C. ; Virmani, Renu. / Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model. In: Journal of the American College of Cardiology. 1994 ; Vol. 24, No. 5. pp. 1398-1405.
@article{642292ba834b40b69d225736cba460c5,
title = "Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model",
abstract = "Objectives. This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. Background. Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. Methods. Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. Results. The area of thrombus was minimal at 24 h ([mean ± SE] 0.44 ± 0.12 mm2). Neointimal area at 7 days (0.72 ± 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 ± 0.39 mm2) and 28 days (3.30 ± 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 ± 3.5{\%} at 7 days compared with 9.6 ± 1.3{\%} by 14 days (p = 0.0247) and declined to 1.1 ± 0.97{\%} by 28 days (p < 0.008, 7 and 14 days vs. 28 days). Conclusions. Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.",
author = "Carter, {Andrew J.} and Laird, {John R.} and Andrew Farb and William Kufs and Wortham, {Dale C.} and Renu Virmani",
year = "1994",
month = "11",
day = "1",
doi = "10.1016/0735-1097(94)90126-0",
language = "English (US)",
volume = "24",
pages = "1398--1405",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "5",

}

TY - JOUR

T1 - Morphologic characteristics of lesion formation and time course of smooth muscle cell proliferation in a porcine proliferative restenosis model

AU - Carter, Andrew J.

AU - Laird, John R.

AU - Farb, Andrew

AU - Kufs, William

AU - Wortham, Dale C.

AU - Virmani, Renu

PY - 1994/11/1

Y1 - 1994/11/1

N2 - Objectives. This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. Background. Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. Methods. Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. Results. The area of thrombus was minimal at 24 h ([mean ± SE] 0.44 ± 0.12 mm2). Neointimal area at 7 days (0.72 ± 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 ± 0.39 mm2) and 28 days (3.30 ± 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 ± 3.5% at 7 days compared with 9.6 ± 1.3% by 14 days (p = 0.0247) and declined to 1.1 ± 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days). Conclusions. Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.

AB - Objectives. This study was performed to define the evolution of lesion morphology and its relation to thrombus formation and smooth muscle cell proliferation after experimental coronary stent placement. Background. Restenosis after percutaneous revascularization may develop because of thrombus accumulation and smooth muscle cell proliferation. In animal models of restenosis, thrombus may assume a significant role in neointimal formation by providing an absorbable matrix into which smooth muscle cells proliferate. Methods. Twenty-eight oversized stents were placed in the coronary arteries of 23 juvenile domestic pigs. The histologic degree of vessel injury, lesion morphometry and smooth muscle cell proliferation measured by immunolocalization with a monoclonal antibody to proliferating cell nuclear antigen (PCNA) were assessed at 24 h and 7, 14 and 28 days after stent placement. Results. The area of thrombus was minimal at 24 h ([mean ± SE] 0.44 ± 0.12 mm2). Neointimal area at 7 days (0.72 ± 0.20 mm2) was similar to the area of thrombus, followed by a significant increase at 14 days (3.15 ± 0.39 mm2) and 28 days (3.30 ± 0.28 mm2) (p < 0.0036, 24 h and 7 days vs. 14 and 28 days). At 14 and 28 days, neointimal thickness correlated with the histologic degree of vessel injury (p < 0.003). In arteries with severe injury, the increase in neointimal thickness is accounted for by replacement of the damaged media. The smooth muscle cell proliferation index was 18.6 ± 3.5% at 7 days compared with 9.6 ± 1.3% by 14 days (p = 0.0247) and declined to 1.1 ± 0.97% by 28 days (p < 0.008, 7 and 14 days vs. 28 days). Conclusions. Early thrombus formation is minimal, and thrombus accounts for a small portion of subsequent neointimal formation. Smooth muscle cell proliferation and matrix formation are the major factors relating to neointimal formation in this proliferative model of restenosis. The evolution of neointimal formation after coronary stenting shows maximal smooth muscle cell proliferation at 7 days, with a decline to low levels by 28 days. Therefore, these data may be useful for developing effective therapies for restenosis.

UR - http://www.scopus.com/inward/record.url?scp=0028051336&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028051336&partnerID=8YFLogxK

U2 - 10.1016/0735-1097(94)90126-0

DO - 10.1016/0735-1097(94)90126-0

M3 - Article

VL - 24

SP - 1398

EP - 1405

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 5

ER -