HART Research Projects

Current research projects within the Hypertension & Renal Theme (HART).

Cardiovascular disease (CVD) is the leading cause of death in adults worldwide, with hypertension and chronic kidney disease (CKD) acting as major risk factors for its development. Alterations in microvascular function and structure have been implicated in the development and progression of both hypertension and CKD, so there is an urgent unmet clinical need for simple non-invasive methods to detect microvascular dysfunction, which might allow earlier identification of patients at increased risk of CVD. It is well recognized that the eye may act as a ‘window’ to the microvasculature.

Chronic kidney disease (CKD) is a risk factor for the development of end-stage kidney disease and cardiovascular disease. In CKD ongoing injury and attempts at self-repair occur simultaneously in the kidney, with disease progressing when the injury exceeds the ability of the kidney to repair. We are using a number of novel pre-clinical models and state-of-the-art technologies to identify pathways that may promote kidney injury or repair, so that we can develop therapies that favour regression of kidney disease.

25-30% of people have salt-sensitive blood pressure (BP), which is an independent risk factor for cardiovascular mortality. Mechanisms underpinning salt sensitive hypertension are not fully understood. However, our recent study (Evans et al, Circulation 2016) has suggested that abnormal glucocorticoid signalling can have a major contributory role in salt sensitivity. This project will systematically analyse hypothalamic-pituitary-adrenal axis function and glucocorticoid metabolism during the adaptation to high salt diets. We will use genetic engineering approaches to understand how high salt intake increases stress hormone production and how this leads to high blood pressure.

Hypertension is highly related with cardiovascular and renal diseases.  Previous blood and urine studies have shown that aldosterone and glucocorticoids are highly related with the renal regulation of blood pressure. The aim of this project is the generation of distribution maps of aldosterone and glucocorticoids on kidney tissue sections with mass spectrometry imaging that will allow us to get better understanding of the renal regulation of blood pressure in combination with the already existing data.

mCCDcl1, a mouse renal cell line, has been shown to be a good model for the study of collecting duct physiology, and cell differentiation. mCCDcl1 cells are cultured on a 3D-printed porous scaffold for the development of a 3D in vitro model of collecting duct.

Too much salt in the diet can lead to an increase in morbidity, whether one is normotensive or hypertensive, but salt-sensitive hypertensives are particularly at risk.

As reported by the Global Burden of Disease Study, kidney disease is one of the fastest rising causes of mortality worldwide, claiming 1.1 million lives per year. A myriad of factors can lead to kidney damage; as a vital organ filtering approximately 180 litres of blood per day, a decline in kidney function is swiftly followed by a decline in health and eventually death. The elucidation of the physiology of the kidney will enable the development of improved therapies and treatments for managing kidney diseases.

Reducing salt intake is a major health policy advocated by The World Health Organization to reduce the global burden of hypertension, Cardiovascular Disease and Chronic Kidney Disease (CKD). Salt restriction is a beneficial lifestyle change for people with cardiovascular and kidney disease but long-term adherence to reduced salt intake is poor.

Kidney disease is a major risk factor for cardiovascular mortality. Multiple genetic and environmental factors provoke susceptibility to kidney disease. We have identified several susceptibility genes using a combination of; high-throughput transcript expression, bioinformatics and renal physiology (1). Historically we found angiotensin converting enzyme (ACE) to be a key modifier of hypertensive renal injury (2). ACE inhibitors have become frontline drugs used everyday in the clinic to tackle hypertension and kidney disease.

Diabetes is the leading cause of renal failure. Inflammation, endothelial dysfunction and microvascular damage are common findings, but causal molecular mechanisms remain poorly understood. We demonstrated previously that renal P2X7 receptor (P2X7R) expression is increased in diabetic patients (DOI: 10.1016/j.ebiom.2017.04.011).