Pericytes in cardiac Electro-Metabolic Signaling

Blood flow in the heart is preferentially directed to regions of high metabolic activity while bypassing less active areas with lower demands. This regulation is believed to be highly localized and finely controlled, mediated by a mechanism termed "Electro-Metabolic Signaling" (EMS), identified in both the brain and heart and presumed to exist in other vascular systems. Four key cellular components—ventricular myocytes, capillary endothelial cells, pericytes, and vascular smooth muscle cells—are thought to contribute significantly to EMS in heart. While each element serves several important roles, our study focuses on cardiac pericytes, a type of mural cell that adorns the capillaries in the heart. The dynamic functions and characteristics of the cardiac pericytes under physiological conditions have been difficult to study due to the continuous movement of the beating heart. To address this, we employed a working heart preparation with an intact vascular system at physiological pressures and temperatures (the cardiac Z-Prep, Zhao et al. PNAS 2020). Using a rapid z-stack protocol with a spinning disk confocal microscope, we visualized and quantitatively characterized cardiac pericytes under "physiological" conditions. High-resolution imaging revealed a number of surprising findings. First, pericytes are highly abundant in native cardiac tissue. Second, these cells exhibit extensive spread along capillaries, with significant extensions that traverse the surfaces of adjacent ventricular myocytes and connect to distant capillaries. The pericyte arms often arise from an identified capillary-based pericyte, travel along the surface of one or more ventricular myocytes and terminate on a distant capillary endothelial cell surface. This anatomical organization suggests that pericytes play likely critical roles in signaling, communication, and contractility within the heart. Although pericytes are considered fragile due to their significant loss during isolation procedures, our findings show that they are remarkably robust in their native environment, enduring the dynamic forces of normal cardiac function. These observations underscore the importance of pericytes in normal heart physiology and provide a foundation for future studies on their roles in health and disease. NIH U19 AI090959 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.