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Updated: Feb 7, 2026
Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
The potential of chronopharmacology for treatment of atherosclerosis
Carla Winter1, Oliver Soehnlein1,2,3
1Institute for Cardiovascular Prevention (IPEK), LMU Munich, Germany.
Purpose Of Review:
Development of atherosclerosis contributes to cardiovascular diseases that still are the leading cause of mortality worldwide. Successful strategies for treating inflammatory aspects of atherosclerotic lesion development are rare. Here, we review new insights into the impact of circadian rhythmicity on atherogenesis and their potential for innovative time-optimized pharmacological treatment strategies.
Recent Findings:
Studies on the circadian clock revealed an extensive influence on immune cell activity. Immune cell functionality and their recruitment to injured tissues exhibit circadian rhythmicity. Many indications that the circadian clock also modulates atherogenesis were given in the past. Transcriptome analysis of the aorta reveals a time-dependent expression profile. Furthermore, deficiency of the core clock proteins Bmal1 and Clock consistently accelerates atherosclerosis. Recent work provided new insights on time-dependent leukocyte recruitment to atherosclerotic lesions and its regulatory mechanisms through the CCR2-CCL2 axis. Based on timed CCR2-CCL2 signaling blockage, an effective chronopharmacological treatment strategy was established to reduce early lesion development with concomitant reduction of systemic side effects.
Summary:
Circadian rhythmicity impacts on the pathogenesis of atherosclerosis. Circadian oscillation in the expression of drug targets may license timed intervention strategies with improved efficacy and lower risk.
Insights
Circadian rhythms influence atherosclerosis development. Targeting the CCR2-CCL2 axis based on timing can reduce lesion progression and side effects, offering a novel chronopharmacological approach.
Area of Science:
- Cardiovascular Research
- Immunology
- Chronobiology
Background:
- Atherosclerosis is a leading cause of global mortality, with limited treatments for its inflammatory aspects.
- Circadian rhythms significantly influence immune cell activity and tissue recruitment.
- Previous research indicated circadian clock modulation of atherogenesis, supported by time-dependent gene expression in the aorta.
Purpose of the Study:
- To review new insights into circadian rhythm's impact on atherogenesis.
- To explore potential innovative time-optimized pharmacological treatments for atherosclerosis.
Main Methods:
- Review of studies on circadian clock influence on immune cells and atherogenesis.
- Analysis of transcriptome data from the aorta.
- Investigation of core clock protein deficiency effects (Bmal1, Clock).
- Examination of time-dependent leukocyte recruitment via the CCR2-CCL2 axis.
Main Results:
- Deficiency of Bmal1 and Clock proteins accelerates atherosclerosis development.
- Circadian rhythmicity affects leukocyte recruitment to atherosclerotic lesions, regulated by the CCR2-CCL2 axis.
- Timed blockade of CCR2-CCL2 signaling effectively reduced early lesion development and systemic side effects.
Conclusions:
- Circadian rhythmicity plays a crucial role in the pathogenesis of atherosclerosis.
- Oscillations in drug target expression allow for timed interventions, potentially improving efficacy and reducing risks.
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