on January 12, 2006
Published online before print January 12, 2006, doi: 10.1161/01.ATV.0000203503.82693.c1
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Submitted on August 19, 2005
Accepted on December 23, 2005
Leukocyte Transglutaminase 2 Expression Limits Atherosclerotic Lesion Size
W. A. Boisvert ;
From Vascular Medicine Research (W.A.B.), Brigham and Women’s Hospital, Harvard Medical School, Cambridge, Mass; the Department of Immunology (L.K.C.), The Scripps Research Institute, La Jolla, Calif; the Department of Medicine (D.M.R., A.S., K.A.J., R.T.), VA/UCSD Medical Center, San Diego, Calif; and the Department of Medicine (A.B., O.Q.), University of California San Diego, La Jolla, Calif.
* To whom correspondence should be addressed. E-mail: rterkeltaub{at}ucsd.edu.
Objective--Transglutaminase 2 (TG2), a broadly expressed regulator of protein cross-linking, wound healing, and tissue fibrosis, mediates apoptotic cell ingestion and transforming growth factor-
release by macrophages and thereby can limit leukocyte-mediated inflammation. In atherosclerosis, oxidative stress and accumulation of unesterified cholesterol stimulate atherosclerotic lesion cell apoptosis. Cell death in advanced atherosclerotic lesions promotes lesion expansion and vulnerable plaques prone to rupture. Hence, we tested the hypothesis that leukocyte TG2 expression limits atherosclerosis.
Methods and Results--We transplanted TG2-/- or TG2+/+ bone marrow into lethally irradiated low-density lipoprotein receptor.
Conclusions--We conclude that macrophage TG2 expression promotes both apoptotic cell clearance and ABCA1 expression in vitro and limits atherosclerotic lesion size in vivo.
Key words: apoptosis • macrophage • ABCA1
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