help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Originally published online as doi:10.2353/ajpath.2008.070633 on March 18, 2008

Published online before print March 18, 2008
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material
Right arrow Correction (v173,p300)
Right arrow All Versions of this Article:
ajpath.2008.070633v1
172/4/1141    most recent
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Li, G.
Right arrow Articles by Sarembock, I. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Li, G.
Right arrow Articles by Sarembock, I. J.
(American Journal of Pathology. 2008;172:1141-1152.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070633

CD40 Ligand Promotes Mac-1 Expression, Leukocyte Recruitment, and Neointima Formation after Vascular Injury

Guohong Li*{dagger}{ddagger}, John M. Sanders*, Melissa H. Bevard§, ZhiQi Sun{dagger}, James W. Chumley{dagger}, Elena V. Galkina{dagger}, Klaus Ley{dagger} and Ian J. Sarembock*{dagger}

From the Cardiovascular Division,* Department of Medicine, the Division of Endocrinology,§ the Robert M. Berne Cardiovascular Research Center,{dagger} and the Department of Biomedical Engineering, University of Virginia Health System, Charlottesville, Virginia; and the Departments of Neurosurgery and Physiology,{ddagger} Louisiana State University Health Sciences Center–Shreveport, Shreveport, Louisiana

High levels of circulating soluble CD40 ligand (sCD40L) are frequently found in patients with hypercholesterolemia, diabetes, ischemic stroke, or acute coronary syndromes, predicting an increased rate of atherosclerotic plaque rupture and restenosis after coronary/carotid interventions. Clinical restenosis is characterized in part by exaggerated neointima formation, but the underlying mechanism remains incompletely understood. This study investigated the role of elevated sCD40L in neointima formation in response to vascular injury in an atherogenic animal model and explored the molecular mechanisms involved. apoE–/– mice fed a Western diet developed severe hypercholesterolemia, significant hyperglycemia, and high levels of plasma sCD40L. Neointima formation after carotid denudation injury was exaggerated in the apoE–/– mice. In vivo, blocking CD40L with anti-CD40L monoclonal antibody attenuated the early accumulation of Ly-6G+ neutrophils and Gr-1+ monocytes (at 3 days) and the late accumulation of Mac-2+ macrophages (at 28 days) in the denudated arteries; it also reduced the exaggerated neointima formation at 28 days. In vitro, recombinant CD40L stimulated platelet P-selectin and neutrophil Mac-1 expression and platelet-neutrophil co-aggregation and adhesive interaction. These effects were abrogated by anti-CD40L or anti-Mac-1 monoclonal antibody. Moreover, recombinant CD40L stimulated neutrophil oxidative burst and release of matrix metalloproteinase-9 in vitro. We conclude that elevated sCD40L promotes platelet-leukocyte activation and recruitment and neointima formation after arterial injury, potentially through enhancement of platelet P-selectin and leukocyte Mac-1 expression and oxidative activity.




This article has been cited by other articles:


Home page
 CirculationHome page
C. Antoniades, T. Van-Assche, C. Shirodaria, J. Diesch, A. S. Antonopoulos, J. Lee, C. Cunnington, D. Tousoulis, C. Stefanadis, B. Casadei, et al.
Preoperative sCD40L Levels Predict Risk of Atrial Fibrillation After Off-Pump Coronary Artery Bypass Graft Surgery
Circulation, September 15, 2009; 120(11_suppl_1): S170 - S176.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
K. Y. Stokes, L. Calahan, C. M. Hamric, J. M. Russell, and D. N. Granger
CD40/CD40L contributes to hypercholesterolemia-induced microvascular inflammation
Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H689 - H697.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
J. M. van Gils, J. J. Zwaginga, and P. L. Hordijk
Molecular and functional interactions among monocytes, platelets, and endothelial cells and their relevance for cardiovascular diseases
J. Leukoc. Biol., February 1, 2009; 85(2): 195 - 204.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2008 by the American Society for Investigative Pathology.