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

doi:10.1016/j.cmet.2018.05.002

Scientific article

English

Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis

Published in

Cell Metabolism, vol. 28, no. 1, p. 175-182.e5

Publication date

2018

Abstract

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.

UNIGE affiliation entities

Not a UNIGE publication

UNIGE research groups

Groupe Christoph Scheiermann (995)

Citation (ISO format)

WINTER, Carla et al. Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis. In: Cell Metabolism, 2018, vol. 28, n° 1, p. 175–182.e5. doi: 10.1016/j.cmet.2018.05.002

Article (Published version)

Identifiers

PID : unige:113705
DOI : 10.1016/j.cmet.2018.05.002
PMID : 29861387

Journal ISSN

1550-4131

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29/11/2018 10:56:00

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29/11/2018 10:56:00

Update

15/03/2023 15:39:10

Status update

15/03/2023 15:39:08

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31/10/2024 12:34:09

Chrono-pharmacological Targeting of the CCL2-CCR2 Axis Ameliorates Atherosclerosis

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Technical informations

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First validation

Update

Status update

Last indexation