Endothelial cells (ECs) that line the interior of blood vessels are subject to constant mechanical stimulation, primarily in the form of shear stress. Mechanosensors on the surface of endothelial cells translate these mechanical stimuli into biochemical signals. When endothelial cells respond appropriately to the physiological range of shear stress, they help to maintain a healthy and quiescent endothelium, contributing to overall homeostasis. On the contrary, when ECs are exposed to altered shear stress, it can trigger pathways leading to pro-inflammatory, pro-coagulant, and oxidative stress responses, ultimately resulting in endothelial dysfunction. This dysfunction is associated with conditions such as myocardial infarction and stroke, which are two leading causes of global mortality.

Altered shear stress is known to induce reactive oxygen species (ROS) in endothelial cells via certain microRNA (miRNAs) mediated pathways. Also, shear stress-induced ROS have been shown to regulate miRNA expression. Understanding the interaction between miRNA and ROS under shear stress in endothelial cells is crucial for comprehending both normal endothelial cell function and dysfunction. This work involves a bioinformatic analysis to identify shear stress-sensitive miRNAs in myocardial infarction and stroke. Following the bioinformatic analysis, experiments will be conducted to determine the changes in the expression of specific miRNAs and levels of reactive oxygen species (ROS) when endothelial cells are cultured in a cone and plate device under defined shear stress conditions. The primary goal of the proposed study is to investigate the crosstalk between shear stress-mediated miRNA and ROS in microvascular and macrovascular endothelial cells. This study may provide new insights into the role of endothelial dysfunction in myocardial infarction and stroke which ultimately helps in the development of microRNA-based therapeutic approaches.