Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis
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Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis. / Winter, Carla; Silvestre-Roig, Carlos; Ortega-Gomez, Almudena; Lemnitzer, Patricia; Poelman, Hessel; Schumski, Ariane; Winter, Janine; Drechsler, Maik; de Jong, Renske; Immler, Roland; Sperandio, Markus; Hristov, Michael; Zeller, Tanja; Nicolaes, Gerry A F; Weber, Christian; Viola, Joana R; Hidalgo, Andres; Scheiermann, Christoph; Soehnlein, Oliver.
In: CELL METAB, Vol. 28, No. 1, 03.07.2018, p. 175-182.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis
AU - Winter, Carla
AU - Silvestre-Roig, Carlos
AU - Ortega-Gomez, Almudena
AU - Lemnitzer, Patricia
AU - Poelman, Hessel
AU - Schumski, Ariane
AU - Winter, Janine
AU - Drechsler, Maik
AU - de Jong, Renske
AU - Immler, Roland
AU - Sperandio, Markus
AU - Hristov, Michael
AU - Zeller, Tanja
AU - Nicolaes, Gerry A F
AU - Weber, Christian
AU - Viola, Joana R
AU - Hidalgo, Andres
AU - Scheiermann, Christoph
AU - Soehnlein, Oliver
N1 - Copyright © 2018 Elsevier Inc. All rights reserved.
PY - 2018/7/3
Y1 - 2018/7/3
N2 - Onset of cardiovascular complications as a consequence of atherosclerosis exhibits a circadian incidence with a peak in the morning hours. Although development of atherosclerosis extends for long periods of time through arterial leukocyte recruitment, we hypothesized that discrete diurnal invasion of the arterial wall could sustain atherogenic growth. Here, we show that myeloid cell recruitment to atherosclerotic lesions oscillates with a peak during the transition from the activity to the resting phase. This diurnal phenotype is regulated by rhythmic release of myeloid cell-derived CCL2, and blockade of its signaling abolished oscillatory leukocyte adhesion. In contrast, we show that myeloid cell adhesion to microvascular beds peaks during the early activity phase. Consequently, timed pharmacological CCR2 neutralization during the activity phase caused inhibition of atherosclerosis without disturbing microvascular recruitment. These findings demonstrate that chronic inflammation of large vessels feeds on rhythmic myeloid cell recruitment, and lay the foundation for chrono-pharmacology-based therapy.
AB - Onset of cardiovascular complications as a consequence of atherosclerosis exhibits a circadian incidence with a peak in the morning hours. Although development of atherosclerosis extends for long periods of time through arterial leukocyte recruitment, we hypothesized that discrete diurnal invasion of the arterial wall could sustain atherogenic growth. Here, we show that myeloid cell recruitment to atherosclerotic lesions oscillates with a peak during the transition from the activity to the resting phase. This diurnal phenotype is regulated by rhythmic release of myeloid cell-derived CCL2, and blockade of its signaling abolished oscillatory leukocyte adhesion. In contrast, we show that myeloid cell adhesion to microvascular beds peaks during the early activity phase. Consequently, timed pharmacological CCR2 neutralization during the activity phase caused inhibition of atherosclerosis without disturbing microvascular recruitment. These findings demonstrate that chronic inflammation of large vessels feeds on rhythmic myeloid cell recruitment, and lay the foundation for chrono-pharmacology-based therapy.
KW - Animals
KW - Atherosclerosis/therapy
KW - Cell Adhesion
KW - Chemokine CCL2/metabolism
KW - Inflammation/pathology
KW - Mesenchymal Stem Cells/metabolism
KW - Mice
KW - Mice, Inbred C57BL
KW - Mice, Knockout
KW - Myeloid Cells/metabolism
KW - Receptors, CCR2/metabolism
KW - Signal Transduction
U2 - 10.1016/j.cmet.2018.05.002
DO - 10.1016/j.cmet.2018.05.002
M3 - SCORING: Journal article
C2 - 29861387
VL - 28
SP - 175
EP - 182
JO - CELL METAB
JF - CELL METAB
SN - 1550-4131
IS - 1
ER -