The Hunt for Novel Prognostic Blood Biomarkers of Hypertension

Student thesis: Doctoral ThesisDoctor of Philosophy (PhD)

Abstract

Hypertension is defined as a chronic state of elevated blood pressure, and results in a significantly increased risk of developing diseases such as; coronary heart disease, kidney damage and stroke. Essential hypertension is a multifactorial and polygenic condition that remains asymptomatic until much of the damage has already been done, resulting in many going undiagnosed (1 in 3) until the health impact has become severe. Globally, hypertension is responsible for 9.4 million deaths every year. Therefore, in order to improve upon the diagnostic assessment of the disease, this current study made use of the Spontaneously Hypertensive Rat (SHR) as a polygenic model of elevated blood pressure. Using an optimised next generation sequencing approach to guide biomarker discovery, transcripts predicted to be significantly regulated between the SHR and its normotensive control were selected as candidate biomarkers of hypertension. The interferon-induced protein with tetratricopeptide repeats 1 (Ifit1) saw a robust elevation in the blood of SHRs at both juvenile and adult ages. This, coupled with its key integretive role in innate immunity, lead to Ifit1 being selected for further validation through a series of environmentally induced forms of elevating blood pressure. Ifit1 performed well as a biomarker of the SHR strain, against a host of normotensive controls. As such, Ifit1 was selected for additional characterisation in the blood through Flow Cytometry as well as assessment in a key integrative region of the brain tasked with cardiovascular control.
Date of Award24 Mar 2020
Original languageEnglish
Awarding Institution
  • The University of Bristol
SupervisorDavid Murphy (Supervisor) & Charles C.T. Hindmarch (Supervisor)

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