Time of the day negatively impacts immune cell myocardial recruitment and cardiac remodeling induced by abdominal aortic constriction in mice

Abstract

Consequences of myocardial infarction are more severe when it occurred in the middle of the day (active phase) rather than in the resting phase; and patients operated in the afternoon displayed fewer cardiovascular events after cardiac surgery than patients operated in the morning, suggesting that circadian rhythm may affect cardiovascular events or cardiac remodeling. Interestingly, the immune system plays a critical role in the myocardial remodeling process, and the heart is submitted to circadian variations of immune cells amount. Our objective is to determine the impact of abdominal aortic constriction surgery (AAC) time of day on the severity of cardiac remodeling and the myocardial immune profile induced by the pressure overload in mice. We compared hearts of AAC (ligation 27G) mice operated in their resting phase, at Zeitgeber time 5 (ZT5 n = 6) and early active phase (ZT13 n = 8) with SHAM mice (ZT5 n = 7; ZT13 n = 7). Animal survival, heart weights, and cardiac immunophenotyping analyzed by flow cytometry were studied one week after AAC. Heart weights of AAC mice were increased 7 days after surgery (+20% at ZT5 and +40% at ZT13; P < 0.05 and P < 0.01 compared to SHAM groups respectively). Immune cell analysis showed a 1.7-fold increase in myocardial leukocyte infiltration in ZT13 vs. ZT5 AAC group (P < 0.05) with increased numbers of total, resident, and monocyte-derived macrophages. Myocardial infiltration of dendritic cells and granulocytes was also greater in AAC ZT13 mice compared with AAC ZT5 mice and SHAM groups. Finally, we showed higher mortality in AAC mice operated at ZT13 (vs. ZT5). Time of day when sustained cardiac pressure overload occurs affected cardiac remodeling one week after the onset of AAC; with more pronounced innate immune cells infiltration and hypertrophy of the myocardium at ZT13 (vs. ZT5). Further explorations are needed to determine the link between the increased number of immune cells and the more severe phenotype observed in the ZT13 group.