Pulmonary Vasculature Redox Signaling in Health and Disease

Karthik Suresh, Larissa A. Shimoda, Suresh, Karthik, Shimoda, Larissa A.

Pulmonary hypertension (PH) refers to a disorder characterized by elevated pulmonary arterial pressure, leading to right ventricular overload and eventually right ventricular failure, which results in high morbidity and mortality. PH is associated with heterogeneous etiologies and distinct molecular mechanisms, including abnormal migration and proliferation of endothelial and smooth muscle cells. Although the exact details are not fully elucidated, reactive oxygen species (ROS) have been shown to play a key role in promoting abnormal function in pulmonary arterial smooth muscle and endothelial cells in PH. In endothelial cells, ROS can be generated from sources such as NADPH oxidase and mitochondria, which in turn can serve as signaling molecules in a wide variety of processes including posttranslational modification of proteins involved in Ca(2+) homeostasis. In this chapter, we discuss the role of ROS in promoting abnormal vasoreactivity and endothelial migration and proliferation in various models of PH. Furthermore, we draw particular attention to the role of ROS-induced increases in intracellular Ca(2+) concentration in the pathobiology of PH.