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Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients

OBJECTIVE: Transplant arteriosclerosis (TA) restricts long-term survival of heart transplant recipients. Although the role of monocyte/macrophages is well established in native atherosclerosis, it has been studied to a much lesser extent in TA. Plasma cholesterol is the most important non-immunologi...

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Autores principales: Schiopu, Alexandru, Nadig, Satish N., Cotoi, Ovidiu S., Hester, Joanna, van Rooijen, Nico, Wood, Kathryn J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423631/
https://www.ncbi.nlm.nih.gov/pubmed/22704806
http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.010
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author Schiopu, Alexandru
Nadig, Satish N.
Cotoi, Ovidiu S.
Hester, Joanna
van Rooijen, Nico
Wood, Kathryn J.
author_facet Schiopu, Alexandru
Nadig, Satish N.
Cotoi, Ovidiu S.
Hester, Joanna
van Rooijen, Nico
Wood, Kathryn J.
author_sort Schiopu, Alexandru
collection PubMed
description OBJECTIVE: Transplant arteriosclerosis (TA) restricts long-term survival of heart transplant recipients. Although the role of monocyte/macrophages is well established in native atherosclerosis, it has been studied to a much lesser extent in TA. Plasma cholesterol is the most important non-immunologic risk factor for development of TA but the underlying mechanisms are largely unknown. We hypothesized that monocyte/macrophages might play an important role in the pathogenesis of TA under hyperlipidemic conditions. METHODS: We studied TA in fully mismatched arterial allografts transplanted into hyperlipidemic ApoE(−/−) recipients compared to wild-type controls. The recruitment of distinct monocyte populations into the grafts was tracked by in vivo labelling with fluorescent microspheres. We used antibody-mediated depletion protocols to dissect the relative contribution of T lymphocytes and monocytes to disease development. RESULTS: In the hyperlipidemic environment the progression of TA was highly exacerbated and the inflammatory CD11b(+)CD115(+)Ly-6C(hi) monocytes were preferentially recruited into the neointima. The number of macrophage-derived foam cells present in the grafts strongly correlated with plasma cholesterol and disease severity. Depletion of Ly-6C(hi) monocytes and neutrophils significantly inhibited macrophage accumulation and disease progression. The accelerated monocyte recruitment occurs through a T cell-independent mechanism, as T cell depletion did not influence macrophage accumulation into the grafts. CONCLUSIONS: Our study identifies for the first time the involvement of inflammatory Ly-6C(hi) monocytes into the pathogenesis of TA, particularly in conditions of hyperlipidemia. Targeted therapies modulating the recruitment and activation of these cells could potentially delay coronary allograft vasculopathy and improve long-term survival of heart transplant recipients.
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spelling pubmed-34236312012-09-05 Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients Schiopu, Alexandru Nadig, Satish N. Cotoi, Ovidiu S. Hester, Joanna van Rooijen, Nico Wood, Kathryn J. Atherosclerosis Article OBJECTIVE: Transplant arteriosclerosis (TA) restricts long-term survival of heart transplant recipients. Although the role of monocyte/macrophages is well established in native atherosclerosis, it has been studied to a much lesser extent in TA. Plasma cholesterol is the most important non-immunologic risk factor for development of TA but the underlying mechanisms are largely unknown. We hypothesized that monocyte/macrophages might play an important role in the pathogenesis of TA under hyperlipidemic conditions. METHODS: We studied TA in fully mismatched arterial allografts transplanted into hyperlipidemic ApoE(−/−) recipients compared to wild-type controls. The recruitment of distinct monocyte populations into the grafts was tracked by in vivo labelling with fluorescent microspheres. We used antibody-mediated depletion protocols to dissect the relative contribution of T lymphocytes and monocytes to disease development. RESULTS: In the hyperlipidemic environment the progression of TA was highly exacerbated and the inflammatory CD11b(+)CD115(+)Ly-6C(hi) monocytes were preferentially recruited into the neointima. The number of macrophage-derived foam cells present in the grafts strongly correlated with plasma cholesterol and disease severity. Depletion of Ly-6C(hi) monocytes and neutrophils significantly inhibited macrophage accumulation and disease progression. The accelerated monocyte recruitment occurs through a T cell-independent mechanism, as T cell depletion did not influence macrophage accumulation into the grafts. CONCLUSIONS: Our study identifies for the first time the involvement of inflammatory Ly-6C(hi) monocytes into the pathogenesis of TA, particularly in conditions of hyperlipidemia. Targeted therapies modulating the recruitment and activation of these cells could potentially delay coronary allograft vasculopathy and improve long-term survival of heart transplant recipients. Elsevier 2012-08 /pmc/articles/PMC3423631/ /pubmed/22704806 http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.010 Text en © 2012 Elsevier Ireland Ltd. https://creativecommons.org/licenses/by/3.0/ Open Access under CC BY 3.0 (https://creativecommons.org/licenses/by/3.0/) license
spellingShingle Article
Schiopu, Alexandru
Nadig, Satish N.
Cotoi, Ovidiu S.
Hester, Joanna
van Rooijen, Nico
Wood, Kathryn J.
Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title_full Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title_fullStr Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title_full_unstemmed Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title_short Inflammatory Ly-6C(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
title_sort inflammatory ly-6c(hi) monocytes play an important role in the development of severe transplant arteriosclerosis in hyperlipidemic recipients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3423631/
https://www.ncbi.nlm.nih.gov/pubmed/22704806
http://dx.doi.org/10.1016/j.atherosclerosis.2012.05.010
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