Abstract P165: Cardiac Capillary Pericytes Constriction Mediates Sleep Deprivation Induced Coronary Microcirculation Dysfunction

Abstract

Background: Lack of sleep can lead to a variety of adverse cardiovascular events and even sudden death. In most cases, there is no obstructive coronary artery. Coronary microcirculation dysfunction (CMD) is thereby thought to play an important role in cardiovascular events caused by sleep loss. Pericytes regulate blood flow and mediate neurovascular signaling in brain. Here, we hypothesized that cardiac capillary pericytes mediate sleep loss related CMD. Methods and Results: Eight-week-old male C57BL/6J mice were deprived sleep for 6 hours or 72 hours. Cardiac function was detected by transthoracic echocardiography before and after sleep deprivation (SD). Vascular endothelial dyes were perfusion before tissue harvest to evaluate cardiac perfusion. By whole heart clearing, 3D immunolabeling and imaging, the effect of pericytes on cardiac capillary was accessed. Acute 6-hours total sleep deprivation or 72-hours severe sleep deprivation led to decreased cardiac systolic and diastolic dysfunction. Left ventricular end diastolic diameter and left ventricular end systolic diameter increased by 10.12% (0.32 mm of 3.14 mm) and 19.00% (0.31 mm of 1.63 mm). Although coronary flow velocity reserve showed no differences between sleep deprivation and control groups, the basal and maximum coronary blood velocity were increased in acute and severe total sleep deprivation mice, which illustrated CMD. Compared with mice in the control group, the area of cardiac perfusion in the sleep deprivation group was significantly reduced (33.42 ± 4.30% vs. 53.81 ± 7.42%, P < 0.05; SD group, n=7; control group, n=6). Whole mount heart imaging showed pericytes were widely distributed around the microvascular, without difference in regional distribution in the heart. In the area of cardiac perfusion defect, capillary blockages colocalized with pericytes, and the capillary diameter at the pericyte body was significantly reduced in sleep deprived mice (2.01 ± 0.12 μm vs. 2.92 ± 0.07 μm, P < 0.05; SD group, n=10; control group, n=10). Conclusion: Sleep restriction led to cardiac dysfunction and CMD, that pericytes mediated contraction of capillaries might contribute to the process. Cardiac pericytes would be a novel therapeutic target in sleep loss associated heart disease.