Disturbance of suprachiasmatic nucleus function improves cardiac repair after myocardial infarction by IGF2-mediated macrophage transition

Circadian Effects on Vascular Immunopathologies

“…In contrast to shift work, disruption of circadian rhythms by surgical lesion of the SCN attenuates MI damage 132 (Figure 2D). In a double-blind experiment, SCN lesions attenuated (≈2-fold) cardiac damage and cardiac fibrosis 4 weeks after MI compared with sham control animals.…”

“…[140][141][142][143][144][145][146][147] In mice, a higher severity is generally observed when infarction occurs at the day-night transition in mice. 35,64,132,[148][149][150][151][152][153][154] The main mouse MI model is generated by temporary or permanent ligation of the left anterior descending (LAD) coronary artery. In one set of experiments, mice were phase-shifted to different time zones and surgeons were blinded to the time of mice, limiting the variable to the time zone of the mouse and not the surgeon.…”

“…Many findings generated in preclinical mouse models do not translate into humans. For example, the association between the time-of-day at symptom onset and the severity of MI has been unequivocal in mice 35,132,[148][149][150][151][152][153] but controversial in patients. [140][141][142][143][144] Given that mice are nocturnal and humans are diurnal, using other-diurnal-animal models to study the circadian rhythms in cardiovascular diseases might be beneficial in aiding the translational potential of studies.…”

“…Consequently, MI as induced by permanent LAD ligation is more severe at ZT13 compared with ZT5. 35,132 The increase in neutrophil infiltration to the heart after MI at ZT13 compared with ZT5 was accompanied by a decrease in neutrophil counts (3-4-fold) and an increase in granulocyte-monocyte progenitors (≈2-fold) in the bone marrow. Furthermore, treatment with the CXCR2 antagonist SB225002 reduced the infiltration of CXCR2 + neutrophils to the heart after MI (≈2-fold) and neutrophil depletion with an anti-Ly6G antibody improved the recovery after MI at ZT13 35 (Figure 2C).…”

“…Circadian desynchronization by constant light had similar effects on MI as SCN lesions in mice. 132 This indicates that a complete lack of circadian oscillations may result in a milder phenotype than an alteration of oscillations, the latter of which may be associated with a higher stress burden. However, why these forms of circadian rhythm disruption (SCN lesion and constant light) result in different effects on MI from shift work remains to be further studied.…”