HSP27 regulation of GPCR-induced vascular inflammation

The vascular endothelium plays a crucial role in maintaining fluid and macromolecule homeostasis through the body as well as propagating inflammatory responses as a result of pathogens and injuries. This process is generally protective and resolves efficiently. However, dysregulation of this process can lead to chronic inflammation in diseases such as diabetes and hypertension, or acute conditions as seen in tissue edema or sepsis, in the presence of bacteria, and can lead to death. Understanding the mechanisms that underlie this balanced regulation and re-establishment of tissue homeostasis after inflammation is important to understand as it has a vast array of therapeutic potential for combating inflammation-driven diseases. G-protein coupled receptors (GPCRs) are often activated by inflammatory mediators in the endothelium and are key modulators leading to endothelial barrier permeability and cytokine production. In this dissertation, I describe a novel mechanism for endothelial GPCR signaling through heat shock protein 27 (HSP27) in the resolution of vascular inflammation after GPCR-induction both in vitro and in vivo