Effects of Src Homolog Phosphatase-1 (SHP-1) on Janus Kinase 2 (JAK/STAT) and Phosphatidylinositol 3-Kinase (PI3-kinase) Pathways in 7 and 28 day Renal-Wrap Hypertension



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Hypertension, or high blood pressure, affects millions of patients every year and is associated with many types of cardiovascular diseases. While there are many drugs available to treat hypertension only 40% of the patients on medication currently have their blood pressure controlled. One problem that contributes to this low effectiveness medication is that there is a paucity of knowledge about the molecular mechanisms involved in the regulation of blood pressure and the process of pathogenesis that leads to end organ damage. For example, the molecular mechanisms involved in increasing blood pressure are not the same ones that maintain the increase over time. In this project we studied the Janus Kinase (JAK)/Signal Transducers of Activated Transcription (STAT) and the Phosphoinositide kinase (PI3-kinase) pathways. These two pathways have been linked to altered function associated with other forms of hypertension but their roles and their regulation in these disease processes are not well understood. We chose to use two time points in our study (7 and 28 days). The reasons for this are to look at development vs established mechanisms. The main purpose of this thesis is to identify the levels of JAK2/STAT and PI3-kinase pathway activity. In this research, male Sprague-Dawley rats will be induced with hypertension by renal wrap and sacrificed at days 7 and 28. Aorta, other blood vessels and cells from these rats will be collected and studied by myography and Western Blot to explore the relationship between the JAK2/STAT and PI3-kinase pathways. These data clearly demonstrate that these pathways are altered during hypertension and result in function changes in the vasculature. Although many drugs being used to treat hypertension are currently available in the market, 60% of the hypertensive patients do not have their disease progression under control which leads to end organ damage. By studying these pathways and their roles, we aim to identify potential new drug targets to control hypertension.



Src Homolog Phosphatase-1 (SHP-1), Janus Kinase 2 (JAK/STAT), Phosphatidylinositol 3-Kinase (PI3-kinase), Renal-Wrap Hypertension