Endothelial Reactive Oxygen Species: Key Players in Cardiovascular Health and Disease

Significance: Endothelial cells (ECs) line the entire vasculature system and serve as both barriers and facilitators of intra- and interorgan communication. Positioned to rapidly sense internal and external stressors, ECs dynamically adjust their functionality. Endothelial dysfunction occurs when the ability of ECs to react to stressors is impaired, which precedes many cardiovascular diseases (CVDs). While EC reactive oxygen species (ROS) have historically been implicated as mediators of endothelial dysfunction, more recent studies highlight the central role of ROS in physiological endothelial signaling. Recent Advances: New evidence has uncovered that EC ROS are fundamental in determining how ECs interact with their environment and respond to stress. EC ROS levels are mediated by external factors such as diet and pathogens, as well as inherent characteristics, including sex and location. Changes in EC ROS impact EC function, leading to changes in metabolism, cell communication, and potentially disrupted signaling in CVDs. Critical Issues: Current endothelial biology concepts integrate the dual nature of ROS, emphasizing the importance of EC ROS in physiological stress adaptation and their contribution to CVDs. Understanding the discrete, localized signaling of EC ROS will be critical in preventing adverse cardiovascular outcomes. Future Directions: Exploring how the EC ROS environment alters EC function and cross-cellular communication is critical. Considering the inherent heterogeneity among EC populations and understanding how EC ROS contribute to this diversity and the role of sexual dimorphism in the EC ROS environment will be fundamental for developing new effective cardiovascular treatment strategies. Antioxid. Redox Signal. 42, 905-932.