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Modulators of the Apelin Receptor

Fitzpatrick, Christopher Mark (2018) Modulators of the Apelin Receptor. PhD thesis, University of Leeds.

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Abstract

The treatment of age and lifestyle related diseases remain at the forefront of modern medicine. Conditions such as strokes and ischemic heart disease contribute to millions of deaths across the world every year, and cancer persists as one of the most prevalent diseases in the world. Hypertension, or high blood pressure, contributes as the largest risk factor for strokes and heart failure. Treatments in this area have been revolutionised since the 1950s, but hypertension remains an issue worldwide – especially in countries with a high obesity rate, and in aging populations. Approximately 1 in 4 adults in the world have high blood pressure, and it was attributed as being directly responsible for 10.7 million deaths worldwide in 2015. The rate of incidence in the UK is even higher than the worldwide average, with nearly 30% of adults estimated to have higher than recommended blood pressure. The need for new and effective treatments is therefore pressing, and may result in saving lives across the world. Cancer represents both one of the most common, and one of the most devastating diseases in the world. From an estimated 14.1 million cases reported in 2012, there were over 8 million fatalities. Even with improving treatments and new methods for combatting the most common forms of cancer, overall prognosis for cancer treatments remains poor, and therapies often take the form of harmful chemo and radiotherapy. In the UK alone, there are over 350,000 new cases of cancer reported each year, and Cancer Research UK estimates that the cancer incidence rate has increased by over 13% since 1990 – due to a combination of extended lifespans and lifestyle changes. This thesis will demonstrate that the apelinergic system – compromised of the APJ receptor and its ligands, the apelin peptides – offers the opportunity for powerful new therapies for both hypertension and various cancer types. The identification of powerful APJ agonists, their characterisation in vivo, and the potential of these compounds to form the basis of new treatments for hypertension will then be reported. Also proposed are methods for the identification of APJ antagonists, with their potential for use as cancer therapies highlighted.

Item Type: Thesis (PhD)
Related URLs:
Keywords: Apelin, APJ, Hypertension, Angiogensis, Cancer, Vasodilation
Academic Units: The University of Leeds > Faculty of Maths and Physical Sciences (Leeds) > School of Chemistry (Leeds)
Depositing User: Mr Christopher Fitzpatrick
Date Deposited: 17 Jan 2019 11:49
Last Modified: 17 Jan 2019 11:49
URI: http://etheses.whiterose.ac.uk/id/eprint/22480

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